IntroductionThe blood group antigens of the ABO and RhD systems play a pivotal role in transfusion medicine because of their role in the safe administration of blood transfusions. In addition, these cell surface antigens have been demonstrated to have direct effects on the susceptibility for several diseases bib9 bib23 bib24. One of the first such studies was published in 1962, demonstrating a relationship between the ABO system and ischemic heart disease bib3. Multiple subsequent studies have revealed associations with a range of diseases, with a prominent example being a decreased risk of thromboembolic events and increased risks of some hemorrhagic events in individuals with blood group O bib9 bib8 bib27. The difference in thrombotic and hemorrhagic phenotypes has been attributed to variability in levels of Factor VIII and von Willebrand factor, where ABO status may explain as much as 30% of this variability bib9 bib19 bib12 bib16 bib18 Other prominent examples include associations with risks of a number of infectious diseases, to the extent that the allele distribution of the blood group antigens has evolved to reflect some areas endemic to these infectious diseases bib11. This is in part true for infectious disease such as Plasmodium falciparum malaria, Helicobacter pylori, and Vibrio cholera, where ABO blood groups are involved in different aspects of pathogenesis, from microbe attachment and entry into cells to subsequent disease development and severity of disease bib23 bib11 bib6 bib7. Surface antigens of the ABO blood groups are defined by the immunodominant, terminal sugar residues on certain glycolipids and glycoproteins anchored to the membrane of red blood cells and exposed extracellularly. Even if expressed from a single-gene locus, the ABO gene on chromosome 9, A and B antigens are present not only on erythroid cells but also in many other tissues, and due to the diverse tissue, expression may result in differences in disease occurrence bib13. The A and B allelic variants of the ABO locus encode the A and B glycosyltransferases, which differ only by a few amino acid residues, add the donor substrates UDP-N-acetylgalactosamine or UDP-galactose, respectively, to a common acceptor substrate, namely a carbohydrate chain terminating with the so-called H antigen, in turn dependent on fucosyltransferase activity expressed from the FUT1 and FUT2 genes on chromosome 19. In blood group O, the H antigen is left unaltered due to lack of ABO enzyme activity, most commonly by a single-nucleotide deletion in the ABO coding region bib22.The RhD antigen, on the other hand, has a less clear link to health outcomes. RhD status has mainly been linked to alloimmunization of the pregnant women with hemolytic disease of the fetus and newborn as a consequence bib25. Beyond these direct effects, little is known about its role in disease pathogenesis. The difference between RhD-positive and -negative blood group is the presence or absence of the RhD protein on the red blood cell surface. However, both individuals with and without RhD possess the homologous RhCE protein and Rh-associated glycoprotein (RhAG) on their red cells. Thus, functions carried out by RhD are likely performed RhCE and RhAG in RhD-negative individuals, and this redundancy may in part explain the scarcity of findings related to RhD status bib1.Using the Scandinavian Donation and Transfusion (SCANDAT) database, we have previously studied associations between ABO blood groups and cancer subtypes, cardiovascular and thromboembolic disease, the occurrence of dementia and degradation of bioprosthetic aortic valves in relation to ABO blood group bib27 bib20 bib28 bib26. However, these and most other prior studies into the association between ABO blood group and disease outcomes have been limited by potentially misdirected a priori hypotheses and phenome-wide disease associations have not been thoroughly explored in a systematic manner. Therefore, in the current study, we aimed to agnostically investigate the association between ABO and RhD blood group and disease occurrence for a large number of disease phenotypes using large-scale population-based Swedish healthcare registries.Materials and methodsStudy population and study designIndividuals in the study were identified using an updated version of the Scandinavian donations and transfusion database (SCANDAT3-S). This database includes close to 8 million individuals who have donated blood, received a blood transfusion, or have had blood group testing done for other reasons. Other reasons for blood group testing would typically be pre-emptive testing for example, before surgery or in antenatal care. The database contains detailed information on blood donations, transfusions, as well as blood group antigen and antibody testing results and is thoroughly described elsewhere bib29. It is nationally complete since 1995, but information dates back to 1968 with various levels of completeness, mainly depending on the geographical region. Using unique national registration numbers assigned to all inhabitants of Sweden, the SCANDAT3-S database has been linked to a range of national health outcomes registers, for hospital care, cancer, cause of death, and drug prescriptions . From SCANDAT3-S, we extracted information on ABO and RhD blood group and created a main cohort and a validation cohort. The main cohort consisted of all individuals who were born in Sweden where at least one parent was born in Sweden and who, for any reason, had undergone ABO and RhD blood group typing with a conclusive result, but who did not donate blood within 90 days of the test. Person-time for blood donors were excluded from the main cohort to maximize the representativeness of the study population. In the validation cohort, we included all individuals in the SCANDAT3-S database who had ever donated blood. As such, an individual could contribute person-time in both cohorts, such as in the case a person started to donate blood more than 90 days later from a blood grouping test that was initially performed for other reasons. The person-time before blood donation would contribute to the main cohort censoring at entry in the validation cohort starting at the time of blood grouping before the blood donation.OutcomesWe defined and studied a large number of disease categories. Non-cancer disease categories were based on discharge diagnoses from the national patient register, which covers all hospital inpatient care in Sweden since 1987 and all specialist outpatient care since 1997, and from the Cause of Death register, which records underlying causes of death for all persons in Sweden since 1964 bib4 bib17. Because the 10th revision of the International Classification of Disease (ICD) was implemented in 1997, we limited outcomes ascertainment to events from 1997 or later to avoid inconsistencies between ICD revisions. Cancer outcomes were based on the Cancer Register, which records all incident cancer cases in Sweden since 1958 bib2. All of these registries are held and maintained by the Swedish National Board of Health and Welfare and have a high level of completeness and accuracy. Dates of death and emigration were obtained from population registers kept by Statistics Sweden.Details of non-cancerous disease categories are presented in Supplementary file 3. Non-cancer diseases were classified into disease categories based on the first three codes of the diagnosis, according to the ICD-10 codebook. We did not consider external causes of disease, traumatic injuries, or symptom-based codes as these were deemed unlikely to be related to blood group antigens. Cancer disease categories were based on anatomical coding using the 7th revision of the ICD for all non-hematological malignancies and the 8th revision of the ICD for hematological malignancies. For details of cancer categories, see Supplementary file 4 (SAS code for cancer disease grouping is available upon request).In total, we considered 1217 distinct disease categories. After database construction, we excluded disease categories with fewer than 50 events before analysis as we would be unlikely to detect sufficient events in the validation cohort in categories with fewer than 50 events in the main cohort.Statistical methodsAll persons were followed from the date of the first blood grouping test, from their 18th birthday, or from January 1, 1997, whichever occurred last. Follow-up was extended until the first incident event in each disease category, emigration, death or December 31, 2017, whichever occurred first. A person could thus be included in follow-up for all disease categories investigated.Descriptive statistics were presented for cohort baseline data. For the main analysis, we used a Poisson regression model. In the model, we incorporated the following covariates: ABO blood group (A, AB, B or O), RhD status (weak or category expression variants were excluded), sex, calendar-period, and age. A restricted cubic spline functions with four or five knots placed according to Harrell’s method were applied to the age and calendar-period covariates bib14. The regression model was fitted separately to each disease category resulting in incidence rate ratios (IRR) for each ABO blood group and RhD status using blood group O and RhD negative as reference, respectively. Wald’s method was used to construct 95% confidence intervals (CI). Equi-dispersion was tested using a Lagrange multiplier test. For disease categories where data demonstrated significant over- or under-dispersion after also performing the same analysis but reducing the number of knots from 5 to 4, analyses were instead run using quasi-Poisson regression.Multiple testing was handled using a two-stage approach. First, in the exploratory analysis using the main cohort, we applied a false discovery rate (FDR) adjustment of raw p-values assuming positive dependency of stochastic ordering between outcomes. Second, in the confirmatory analysis using the validation cohort, we used the disease categories with significant effects from explorative analysis, with results presented both without adjustment and using a Bonferroni adjustment. In effect, this allowed us to limit type one errors presenting confirmed associations with high certainty, but still not to compromise type two errors for future confirmatory analysis in other cohorts.ResultsCharacteristics of the main and validation cohorts are presented in Table 1. When combining the main and validation cohort, there were a total of 5.1 million unique individuals. The main cohort consisted of 4.2 million individuals who at any point had undertaken an ABO and RhD blood antigen test. The distribution of A, AB, B, and O were 47%, 5%, 10%, and 38%, respectively, and 84% of individuals were RhD positive. Women constituted 60% of the cohort. The median age at cohort entry was 52 years (interquartile range [IQR], 30–71) and the median year of birth was 1949 (IQR, 1931–1971).header  Main cohort Validation cohort   Number 4,204,234 1,197,522   Age, median (IQR)     Age, median (IQR) 52 (30-71) 30 (23-41) Year of birth, median (IQR) 1949 (1931–1971) 1966 (1953–1978) Sex, % 60 49   Blood group, %     A 47 45   AB 5 5   B 10 11   O 38 39   RhD positive, % 84 82   table1 Table 1. Baseline characteristics of main and validation cohort.Not accounting for censoring due to disease events, the main cohort accrued a total of 49.9 million person-years of follow-up, 23.7 million in blood group A, 2.3 million in blood group AB, 4.9 million in blood group B, and 18.9 million in blood group O.Of the original 1217 disease categories, 1090 remained available for analyses after excluding disease categories with fewer than 50 events. The median number of events per disease category in the main cohort was 4748 (IQR, 869–231,166). A meta-summary of results of regression analyses is presented in Table 2, and graphically in the form of a volcano plot in Figure 1 (also, as an interactive, online variant as Supplementary file 1). Alternatively, results are also presented as an ICD chapter-based, variant Manhattan plot in Figure 2 (also as an interactive, online variant as Supplementary file 2). Overall, in the main cohort and before FDR adjustment for multiple testing, there were 343 and 98 statistically significant associations for the ABO and RhD blood group systems and unique disease categories, respectively. Of these, a total of 143 (41%) and 13 (13%) associations between blood group and unique outcome remained statistically significant for ABO and RhD blood group systems, respectively, after FDR adjustment. For the ABO system, IRRs for statistically significant associations after FDR adjustment ranged from 0.57 to 0.99 for negative associations and from 1.01 to 1.52 for positive associations. For RhD status, IRRs ranged from 0.90 to 0.97 for negative associations and from 1.02 to 1.08 for positive associations. Details of all associations identified after FDR are presented in Supplementary file 5 (for ABO blood groups) and Supplementary file 6 (for RhD).import numpy as np
import pandas as pd
import plotly.graph_objects as go python nulldf = pd.read_csv('df.csv')
df_r = pd.read_csv('df_r.csv')
concordant = pd.read_csv('concordant.csv')

fig = go.Figure()
fdr_p=df['fdr_p']


grp=df['bg'].unique().tolist()
for groups in grp:
        data_filtered=df[(df.bg==groups) & (df.fdr_p < 0.05)]
        fig.add_trace(go.Scatter(x=data_filtered['x'], 
                         y=data_filtered['y'], 
                         mode='markers',
                             opacity=0.5,
                         marker=dict(color=data_filtered['color'],line=dict(color='white',width=0)),
                         text=data_filtered['bg_cat'],
                         customdata=data_filtered['event_pyrs'],
                         hovertext=data_filtered['fdr_p'],
                        meta=data_filtered['combined'],
                        hovertemplate = "<b>%{text}</b>" +
                         "<br>FDR-P: %{hovertext:,.2g}:" +
                         #"<br>IRR: %{marker.size:,.2f}"+
                         "<br>IRR (95% CI): %{meta}" +
                         "<br>Events/Person-years: %{customdata}" +
                         "<extra></extra>",
                         marker_size=(8*data_filtered['irr']),
                         name=groups
                        )
              )



df_r2=df_r[df_r.fdr_p<0.05]
fig.add_trace(go.Scatter(x=df_r2['x'], 
                         y=df_r2['y'], 
                         mode='markers',
                             opacity=0.5,
                         marker=dict(color=df_r2['color'],opacity=df_r2['opacity'],line=dict(color='white',width=0)),
                         text=df_r2['bg_cat'],
                         customdata=df_r2['event_pyrs'],
                         hovertext=df_r2['fdr_p'],
                        meta=df_r2['combined'],
                        hovertemplate = "<b>%{text}</b>" +
                         "<br>FDR-P: %{hovertext:,.2g}:" +
                         #"<br>IRR: %{marker.size:,.2f}"+
                         "<br>IRR (95% CI): %{meta}" +
                         "<br>Events/Person-years: %{customdata}" +
                         "<extra></extra>",
                         marker_size=(8*df_r2['irr']),
                         name='RhD positive'
                        )
              )
              
fig.add_trace(go.Scatter(x=pd.concat([df_r.x[(df_r.fdr_p>=0.05)],df.x[(df.fdr_p>=0.05)]]), 
                         y=pd.concat([df_r.y[(df_r.fdr_p>=0.05)],df.y[(df.fdr_p>=0.05)]]), 
                         mode='markers',
                             opacity=0.7,
                         marker=dict(color=pd.concat([df_r.color[(df_r.fdr_p>=0.05)],df.color[(df.fdr_p>=0.05)]]),opacity=0.7,line=dict(color='white',width=0)),
                         name='Non-significant ABO and RhD',
                         showlegend=True,
                        )
              )
    
    

fig.add_trace(go.Scatter(x=concordant.x, 
                         y=concordant.y, 
                         mode='markers',
                             opacity=0.8,
                         marker=dict(color='black',opacity=0.8,line=dict(color='white',width=0)),
                         text=concordant['bg_cat'],
                         customdata=concordant['event_pyrs'],
                         hovertext=concordant['pvalue'],
                        meta=concordant['combined'],
                        hovertemplate = "<b>%{text}</b>" +
                         "<br>P-value: %{hovertext:,.2g}:" +
                         "<br>IRR: %{marker.size:,.2f}"+
                         "<br>IRR (95% CI): %{meta}" +
                         "<br>Events/Person-years: %{customdata}" +
                         "<extra></extra>",
                         marker_size=(5*concordant['irr']),
                         name='Concordant between Main and Donor cohort, ABO and RhD'
                        )
              )


fig.add_shape(
       # Line Horizontal
          type="line",
         x0=-0.8,
        x1=0.8,
        y0=-(np.log10(0.05)),
        y1=-(np.log10(0.05)),
           line=dict(
              color="black",
             width=0.5,
            dash="dot"
       ), opacity=1,
)
   
    
#Layout
fig.update_layout(title='<b>Volcanoplot showing Incidence Rate Ratios/False Discovery Rate Adjusted P-Values Depending On ABO Blood Group and RhD Status'
                  ''
                  '<br>',
                  title_font_color = '#333333',
                  title_font_size = 14,
                  
                  font=dict(family="helvetica"),
                  
                  xaxis_title='<b>IRR',
                  xaxis_visible=True,
                  xaxis_showline=True,

                  #xaxis_type='category',
                  xaxis_gridcolor='white',
                  #xaxis_tickangle = 90,
                  xaxis_range=[-0.8,0.8],
                  xaxis_showgrid=False,
                  xaxis_tickvals=[-0.5, 0, 0.5],
                  xaxis_linecolor='black',
                  
                  plot_bgcolor='white',
                  showlegend=True,
                  legend= {'itemsizing': 'constant'},
                  hoverlabel=dict(
                        bgcolor="white", 
                        font_size=18, 
                        font_family="helvetica"),
                  
                  yaxis_ticks=('outside'),
                  yaxis_tickwidth=1,
                  yaxis_ticklen=5,
                  yaxis_title='<b>-log10(FDR-adjusted p-value)',
                  yaxis_showline=True,
                  yaxis_showgrid=False,
                  yaxis_visible=True,
                  yaxis_linewidth=1,
                  yaxis_linecolor='black',
                  yaxis_range=[-5,140],
                  #yaxis_tickangle = 90,
                  yaxis_tickvals=[-(np.log10(0.05)),50, 100],
                  yaxis_ticktext=['FDR-P 0.05',50,100],
                  #yaxis_ticksuffix='%',
                  
                  width=1200,
                  height=900
                  )

fig.show() python fig1 Figure 1. Volcano plot of all findings from main and validation cohort.  Volcano plot depicting spread of p-values of significant and non-significant ABO and RhD blood groups for main cohort and validated results. The labels represent the nine findings with the lowest p-value in the validation cohort. 8 application/vnd.plotly.v1+json https://plot.ly 110.0/23680000.0 2575.0/23650000.0 1857.0/23670000.0 6979.0/23640000.0 3498.0/23650000.0 10391.0/23660000.0 315.0/23680000.0 16529.0/23520000.0 5235.0/23580000.0 17105.0/23580000.0 44766.0/23370000.0 50400.0/23370000.0 1103.0/23680000.0 28811.0/23530000.0 119781.0/23250000.0 19188.0/23570000.0 18124.0/23520000.0 20884.0/23500000.0 5425.0/23630000.0 56909.0/23190000.0 153031.0/22630000.0 70329.0/23450000.0 9782.0/23630000.0 10345.0/23600000.0 123807.0/22700000.0 11052.0/23630000.0 27973.0/23620000.0 284515.0/21700000.0 134179.0/22810000.0 30868.0/23420000.0 30777.0/23420000.0 15003.0/23500000.0 14747.0/23510000.0 6899.0/23610000.0 3083.0/23650000.0 76086.0/23040000.0 2707.0/23650000.0 431328.0/20810000.0 150234.0/22380000.0 160247.0/22890000.0 222693.0/22620000.0 47762.0/23460000.0 9522.0/23650000.0 21801.0/23550000.0 49161.0/23400000.0 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12890.0/23580000.0 291.0/23680000.0 2096.0/23660000.0 7590.0/23670000.0 28721.0/23450000.0 37292.0/23380000.0 35680.0/23050000.0 21466.0/22890000.0 8696.0/23530000.0 7359.0/23590000.0 9589.0/23660000.0 <b>%{text}</b><br>FDR-P: %{hovertext:,.2g}:<br>IRR (95% CI): %{meta}<br>Events/Person-years: %{customdata}<extra></extra> 0.02293802559719567 0.00013941181374085105 0.00007300984608716175 1.8196372248450512e-16 0.022056113577998117 0.0252347621063933 0.0042506638207039 0.0004586534045232676 0.003337416375269762 3.8410250306581805e-12 0.007792966407587427 7.669771134145466e-12 0.011299396621767724 6.879062643844708e-12 2.4622538258750725e-8 5.788271064730156e-28 0.000875530669332288 4.4416754998274993e-11 0.0497253763285969 2.996631282347816e-11 9.800789646031263e-42 1.6961649922784994e-19 0.033882939676894125 0.00000658870869538009 1.883335223660511e-39 0.003207935046810969 0.01671935731967564 0.02534022173708447 9.305491592398458e-11 0.007404380098461815 0.014786978703750097 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0.000010762118259698724 0.01023360260614935 5.0447789052433664e-33 0.02200486366390021 2.5252517858055945e-16 0.0003171304023346398 0.01969959211754981 0.0000051009266594339544 0.00003006620886374865 0.007222077945545772 0.016061333260174226 0.04131845993467484 0.000012969645820574765 0.00033546538874346164 0.011299396621767724 0.02195297813929367 0.034444634348768814 2.639758000079009e-14 0.0003472664640193846 4.477296530327382e-11 0.0001324901052159423 0.0036001979934406733 0.035026276376422416 0.0005818505604396704 6.950274775414566e-49 0.00005946172815666035 0.00000973781831723126 6.809097304486495e-10 0.002841471735951429 0.00018264736732168514 0.00039689319810017797 0.021620813767578653 #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f white 0 13.76 9.2 9.52 6.88 7.36 8.4 11.36 8.4 7.44 7.28 7.76 8.48 7.28 7.52 8.24 9.2 7.68 7.44 7.52 8.48 8.56 8.48 8.4 7.36 8.64 7.6 7.76 8.08 8.32 8.32 8.24 8.4 8.72 8.48 9.52 8.16 9.04 7.92 8.24 8.32 8.32 10.48 8.56 8.32 8.16 8.24 8.16 8.32 7.6 8.24 8.32 8.56 9.44 11.04 10.72 8.64 9.28 8.32 8.4 8.08 8.64 8.16 8.24 8.48 8.48 7.6 7.76 7.36 6.72 7.84 7.6 7.84 7.44 7.6 7.44 8.48 8.24 8.48 7.44 8.48 7.6 7.68 7.44 7.76 8.88 8.16 8.24 8.08 8.16 7.76 7.52 7.68 7.6 7.52 7.52 7.6 7.84 8.24 6.16 6.96 11.04 7.68 7.68 8.48 8.32 8.4 8.48 8.4 1.72(1.23-2.39) 1.15(1.08-1.22) 1.19(1.11-1.28) 0.86(0.83-0.89) 0.92(0.88-0.97) 1.05(1.02-1.08) 1.42(1.18-1.71) 1.05(1.03-1.08) 0.93(0.89-0.96) 0.91(0.89-0.94) 0.97(0.96-0.99) 1.06(1.04-1.07) 0.91(0.86-0.96) 0.94(0.92-0.95) 1.03(1.02-1.04) 1.15(1.12-1.18) 0.96(0.94-0.98) 0.93(0.91-0.95) 0.94(0.91-0.98) 1.06(1.04-1.07) 1.07(1.06-1.08) 1.06(1.05-1.07) 1.05(1.02-1.08) 0.92(0.89-0.95) 1.08(1.07-1.1) 0.95(0.92-0.97) 0.97(0.95-0.99) 1.01(1.0-1.02) 1.04(1.03-1.05) 1.04(1.02-1.06) 1.03(1.01-1.05) 1.05(1.02-1.08) 1.09(1.06-1.12) 1.06(1.02-1.1) 1.19(1.12-1.25) 1.02(1.01-1.04) 1.13(1.06-1.2) 0.99(0.98-0.99) 1.03(1.02-1.04) 1.04(1.03-1.05) 1.04(1.03-1.05) 1.31(1.29-1.33) 1.07(1.03-1.1) 1.04(1.02-1.06) 1.02(1.01-1.04) 1.03(1.02-1.04) 1.02(1.01-1.03) 1.04(1.04-1.05) 0.95(0.93-0.97) 1.03(1.02-1.04) 1.04(1.03-1.05) 1.07(1.05-1.09) 1.18(1.15-1.21) 1.38(1.36-1.4) 1.34(1.31-1.38) 1.08(1.06-1.09) 1.16(1.13-1.2) 1.04(1.02-1.06) 1.05(1.02-1.08) 1.01(1.01-1.02) 1.08(1.05-1.1) 1.02(1.01-1.03) 1.03(1.01-1.04) 1.06(1.03-1.09) 1.06(1.04-1.07) 0.95(0.93-0.97) 0.97(0.95-0.99) 0.92(0.9-0.93) 0.84(0.83-0.86) 0.98(0.97-0.99) 0.95(0.94-0.96) 0.98(0.96-0.99) 0.93(0.92-0.94) 0.95(0.94-0.96) 0.93(0.92-0.94) 1.06(1.03-1.1) 1.03(1.02-1.04) 1.06(1.03-1.1) 0.93(0.92-0.94) 1.06(1.02-1.09) 0.95(0.94-0.96) 0.96(0.94-0.98) 0.93(0.89-0.97) 0.97(0.96-0.98) 1.11(1.06-1.15) 1.02(1.01-1.04) 1.03(1.01-1.05) 1.01(1.0-1.02) 1.02(1.01-1.03) 0.97(0.95-0.98) 0.94(0.91-0.98) 0.96(0.94-0.99) 0.95(0.92-0.98) 0.94(0.93-0.95) 0.94(0.91-0.97) 0.95(0.93-0.96) 0.98(0.97-0.99) 1.03(1.01-1.05) 0.77(0.65-0.91) 0.87(0.82-0.93) 1.38(1.32-1.44) 0.96(0.94-0.97) 0.96(0.95-0.98) 1.06(1.04-1.07) 1.04(1.02-1.06) 1.05(1.03-1.08) 1.06(1.03-1.09) 1.05(1.02-1.09) markers A 0.5 A/Measles A/Other disorders of middle ear and mastoid A/Portal vein thrombosis A/Peptic ulcer, site unspecified A/Femoral hernia A/Hepatic failure, not elsewhere classified A/Obstetric embolism A/Urothelial cancer A/Other endocrine  cancer A/Viral and other specified intestinal infections A/Other gastroenteritis and colitis of infectious and unspecified origin A/Erysipelas A/Other specified infectious agents as the cause of diseases classified A/Acute posthaemorrhagic anaemia A/Other anaemias A/Other coagulation defects A/Other nontoxic goitre A/Thyrotoxicosis [hyperthyroidism] A/Thyroiditis A/Type 1 diabetes mellitus A/Type 2 diabetes mellitus A/Unspecified diabetes mellitus A/Other disorders of pancreatic internal secretion A/Hyperparathyroidism and other disorders of parathyroid gland A/Disorders of lipoprotein metabolism and other lipidaemias A/Disorders of mineral metabolism A/Vascular dementia A/Senile cataract A/Other retinal disorders A/Retinal disorders in diseases classified elsewhere A/Otitis externa A/Nonsuppurative otitis media A/Suppurative and unspecified otitis media A/Perforation of tympanic membrane A/Other disorders of tympanic membrane A/Conductive and sensorineural hearing loss A/Postprocedural disorders of ear and mastoid process, not elsewhere A/Essential (primary) hypertension A/Angina pectoris A/Acute myocardial infarction A/Chronic ischaemic heart disease A/Pulmonary embolism A/Other pulmonary heart diseases A/Nonrheumatic mitral valve disorders A/Nonrheumatic aortic valve disorders A/Cardiac arrest A/Atrial fibrillation and flutter A/Heart failure A/Intracerebral haemorrhage A/Cerebral infarction A/Atherosclerosis A/Other peripheral vascular diseases A/Arterial embolism and thrombosis A/Phlebitis and thrombophlebitis A/Other venous embolism and thrombosis A/Varicose veins of lower extremities A/Other disorders of veins A/Hypotension A/Acute tonsillitis A/Pneumonia, organism unspecified A/Chronic diseases of tonsils and adenoids A/Other chronic obstructive pulmonary disease A/Asthma A/Other interstitial pulmonary diseases A/Pleural effusion, not elsewhere classified A/Oesophagitis A/Other diseases of oesophagus A/Gastric ulcer A/Duodenal ulcer A/Gastritis and duodenitis A/Inguinal hernia A/Paralytic ileus and intestinal obstruction without hernia A/Diverticular disease of intestine A/Other diseases of anus and rectum A/Haemorrhoids and perianal venous thrombosis A/Fibrosis and cirrhosis of liver A/Cholelithiasis A/Intestinal malabsorption A/Other diseases of digestive system A/Lichen simplex chronicus and prurigo A/Skin changes due to chronic exposure to nonionizing radiation A/Gout A/Other crystal arthropathies A/Coxarthrosis [arthrosis of hip] A/Ankylosing spondylitis A/Other spondylopathies A/Other intervertebral disc disorders A/Dorsalgia A/Other soft tissue disorders, not elsewhere classified A/Calculus of kidney and ureter A/Calculus of lower urinary tract A/Neuromuscular dysfunction of bladder, not elsewhere classified A/Other disorders of bladder A/Gestational [pregnancy-induced] hypertension A/Premature separation of placenta [abruptio placentae] A/Postpartum haemorrhage A/Single spontaneous delivery A/Maternal infectious and parasitic diseases classifiable elsewhere but A/Congenital malformations of oesophagus A/Cystic kidney disease A/Pancreatic cancer A/Colon cancer A/Non-melanoma cancer A/Breast cancer A/Cervix cancer A/Corpus cancer A/Ovarian cancer A/CUP 0.2355284469075489 0.06069784035361165 0.07554696139253074 -0.06550154875643227 -0.03621217265444472 0.02118929906993809 0.15228834438305647 0.02118929906993809 -0.03151705144606486 -0.040958607678906384 -0.013228265733755159 0.025305865264770258 -0.040958607678906384 -0.02687214640030136 0.012837224705172215 0.06069784035361165 -0.017728766960431602 -0.03151705144606486 -0.02687214640030136 0.025305865264770258 0.02938377768520967 0.025305865264770258 0.02118929906993809 -0.03621217265444472 0.03342375548694973 -0.022276394711152253 -0.013228265733755159 0.004321373782642578 0.01703333929878037 0.01703333929878037 0.012837224705172215 0.02118929906993809 0.03742649794062367 0.025305865264770258 0.07554696139253074 0.008600171761917571 0.05307844348341968 -0.004364805402450088 0.012837224705172215 0.01703333929878037 0.01703333929878037 0.11727129565576427 0.02938377768520967 0.01703333929878037 0.008600171761917571 0.012837224705172215 0.008600171761917571 0.01703333929878037 -0.022276394711152253 0.012837224705172215 0.01703333929878037 0.02938377768520967 0.07188200730612536 0.13987908640123647 0.12710479836480765 0.03342375548694973 0.06445798922691845 0.01703333929878037 0.02118929906993809 0.004321373782642578 0.03342375548694973 0.008600171761917571 0.012837224705172215 0.025305865264770258 0.025305865264770258 -0.022276394711152253 -0.013228265733755159 -0.03621217265444472 -0.07572071393811836 -0.00877392430750515 -0.022276394711152253 -0.00877392430750515 -0.03151705144606486 -0.022276394711152253 -0.03151705144606486 0.025305865264770258 0.012837224705172215 0.025305865264770258 -0.03151705144606486 0.025305865264770258 -0.022276394711152253 -0.017728766960431602 -0.03151705144606486 -0.013228265733755159 0.04532297878665748 0.008600171761917571 0.012837224705172215 0.004321373782642578 0.008600171761917571 -0.013228265733755159 -0.02687214640030136 -0.017728766960431602 -0.022276394711152253 -0.02687214640030136 -0.02687214640030136 -0.022276394711152253 -0.00877392430750515 0.012837224705172215 -0.11350927482751813 -0.060480747381381476 0.13987908640123647 -0.017728766960431602 -0.017728766960431602 0.025305865264770258 0.01703333929878037 0.02118929906993809 0.025305865264770258 0.02118929906993809 1.6394439669554841 3.8557004226148313 4.136618567099093 15.740015187263365 1.656471010496278 1.598000785099808 2.3715432414423288 3.338515378434197 2.4765896074892084 11.415552862675671 2.1082971958294503 11.115217595198436 1.9469447468557937 11.162470735651109 7.608667179067246 27.23745113906647 3.0577286362298937 10.352453173338684 1.30342192138976 10.52336669111941 41.00873893195053 18.77053190458466 1.4700189174065723 5.181199693360894 38.72507237099319 2.4937744337473373 1.7767804205502842 1.596189589185376 10.031260678930144 2.1305112951558325 1.830120552597344 2.3925457665718577 8.37365113399276 1.3610848452996476 7.050741129415144 2.260136440615008 2.53558801045408 2.277384255521252 4.533547560926653 12.463182359636694 16.299276274952632 247.94414013709462 2.4937744337473373 2.679137439354029 1.4677489699941555 3.332696478815832 6.391927133086423 29.416249683724054 4.235628801440129 7.9754362538368335 12.622082187415955 10.352453173338684 33.59040716486513 239.82390874094432 102.67028689052894 23.822611338497854 21.864624153268593 5.064523889910164 1.7978442828615018 2.1981439073773577 7.097187090476315 2.2425754315982016 3.201646766434877 2.420548802102632 8.144962509087131 4.725659674844427 1.5338450838308546 26.09396800220725 66.3304532405828 1.4057393089111134 15.18144510516409 1.8001588557947827 28.99536275397272 9.619670984824658 26.380552203492357 2.6186619614546798 4.968102240011844 1.9899714516698799 32.297157862595924 1.6574813178621923 15.597695313096068 3.498762121475725 1.7055427658653732 5.292350920662522 4.5219213299092536 2.1413378286843594 1.7942184065353426 1.38385587433386 4.887071883612929 3.4743522810184686 1.9469447468557937 1.6585065550698301 1.4628784211935837 13.57843588526943 3.459337155055376 10.3489841414396 3.8778165550145554 2.4436736144843105 1.4556060298284248 3.2351885430307123 48.15799802546925 4.225762472897732 5.01153833253812 9.166910459550603 2.5464566595141584 3.7383865833256205 3.4013263439068244 1.6651279640312775 283.0/2330000.0 196.0/2330000.0 650.0/2330000.0 134.0/2330000.0 5068.0/2300000.0 2794.0/2320000.0 2021.0/2320000.0 2040.0/2310000.0 5755.0/2280000.0 15212.0/2230000.0 7083.0/2310000.0 991.0/2320000.0 11698.0/2240000.0 1029.0/2330000.0 767.0/2330000.0 1469.0/2320000.0 15953.0/2250000.0 21856.0/2230000.0 5013.0/2310000.0 25274.0/2250000.0 12168.0/2270000.0 9619.0/2290000.0 9762.0/2310000.0 1732.0/2320000.0 7064.0/2280000.0 1700.0/2320000.0 5191.0/2280000.0 1241.0/2320000.0 3845.0/2320000.0 3355.0/2320000.0 3625.0/2310000.0 2250.0/2320000.0 6870.0/2270000.0 1281.0/2320000.0 7562.0/2280000.0 4176.0/2300000.0 4885.0/2290000.0 1181.0/2320000.0 9665.0/2240000.0 1554.0/2320000.0 7848.0/2300000.0 2934.0/2310000.0 7722.0/2280000.0 1855.0/2330000.0 23192.0/2170000.0 5708.0/2280000.0 601.0/2330000.0 1067.0/2320000.0 322.0/2330000.0 2428.0/2310000.0 22775.0/2080000.0 3522.0/2300000.0 739.0/2330000.0 3623.0/2300000.0 3589.0/2270000.0 898.0/2320000.0 <b>%{text}</b><br>FDR-P: %{hovertext:,.2g}:<br>IRR (95% CI): %{meta}<br>Events/Person-years: %{customdata}<extra></extra> 0.0020521377112524834 0.018660738926095218 0.000008619381634322138 0.01243961841861932 0.00004906166542925342 0.0012288183580517107 5.0679933373850754e-14 0.010675294635760179 0.00005250168674437825 1.856171098132651e-12 2.500660511659257e-7 0.043621869162074015 0.01278026022864937 0.022561745917871703 0.002858989500812202 0.014914900985038563 0.0004586534045232676 0.005932979599856991 4.56677032800398e-92 0.0024357699843578725 0.005867752497823293 0.006775925674836882 0.001149804395021431 3.0416298146853794e-16 1.7443847605123075e-195 2.3779813138779153e-38 0.00016324164063122619 4.6384569246046237e-10 0.043621869162074015 0.027745626779485524 0.0000015271241470783537 2.905279466573199e-14 0.00946306701223755 0.002621624129443445 9.142094529501984e-9 0.016493518435881257 4.587939335936316e-24 0.03095357281711927 0.006018951711263344 0.021011131096213453 1.6792912342440948e-7 0.023661377567180786 0.000016216108200905655 0.029556618189577805 0.02262451687630024 7.284823857222527e-7 0.0008430767515183032 0.004113991205131898 0.003076202052314497 0.0006426834268697969 0.02817649930268847 0.015886605072118587 1.2846460342289194e-10 0.04140929060926235 0.00041896092807372303 0.0030460491546073364 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 white 0 10.32 10.32 6.48 5.92 8.64 7.36 9.84 7.36 8.64 8.64 8.64 7.2 8.4 7.2 9.36 8.8 8.4 8.32 11.2 8.24 8.32 8.32 8.4 10.16 12.16 11.52 8.56 9.92 8.4 8.48 7.2 6.64 7.6 9.04 7.36 7.6 6.8 8.8 8.4 8.72 7.44 8.56 7.52 8.72 8.24 8.72 9.04 7.52 9.12 7.44 7.76 8.4 10.96 7.6 8.64 8.8 1.29(1.13-1.46) 1.29(1.11-1.49) 0.81(0.75-0.88) 0.74(0.62-0.88) 1.08(1.05-1.11) 0.92(0.88-0.96) 1.23(1.17-1.3) 0.92(0.88-0.96) 1.08(1.05-1.12) 1.08(1.06-1.1) 1.08(1.05-1.11) 0.9(0.84-0.96) 1.05(1.02-1.07) 0.9(0.84-0.96) 1.17(1.08-1.27) 1.1(1.04-1.17) 1.05(1.03-1.07) 1.04(1.02-1.06) 1.4(1.35-1.44) 1.03(1.02-1.05) 1.04(1.02-1.06) 1.04(1.02-1.07) 1.05(1.02-1.07) 1.27(1.2-1.33) 1.52(1.48-1.57) 1.44(1.37-1.52) 1.07(1.04-1.11) 1.24(1.16-1.31) 1.05(1.02-1.09) 1.06(1.02-1.1) 0.9(0.87-0.94) 0.83(0.79-0.87) 0.95(0.93-0.98) 1.13(1.06-1.2) 0.92(0.89-0.94) 0.95(0.92-0.98) 0.85(0.82-0.87) 1.1(1.04-1.17) 1.05(1.02-1.07) 1.09(1.04-1.15) 0.93(0.9-0.95) 1.07(1.03-1.11) 0.94(0.91-0.96) 1.09(1.03-1.15) 1.03(1.01-1.05) 1.09(1.06-1.12) 1.13(1.07-1.2) 0.94(0.91-0.97) 1.14(1.07-1.22) 0.93(0.9-0.96) 0.97(0.96-0.99) 1.05(1.02-1.08) 1.37(1.26-1.5) 0.95(0.92-0.98) 1.08(1.04-1.12) 1.1(1.05-1.16) markers AB 0.5 AB/Other disorders of middle ear and mastoid AB/Portal vein thrombosis AB/Peptic ulcer, site unspecified AB/Thyroid Well-diff  cancer AB/Erysipelas AB/Acute posthaemorrhagic anaemia AB/Other coagulation defects AB/Thyrotoxicosis [hyperthyroidism] AB/Type 1 diabetes mellitus AB/Type 2 diabetes mellitus AB/Unspecified diabetes mellitus AB/Hyperparathyroidism and other disorders of parathyroid gland AB/Disorders of lipoprotein metabolism and other lipidaemias AB/Disorders of mineral metabolism AB/Other disorders of eye and adnexa AB/Suppurative and unspecified otitis media AB/Acute myocardial infarction AB/Chronic ischaemic heart disease AB/Pulmonary embolism AB/Heart failure AB/Cerebral infarction AB/Sequelae of cerebrovascular disease AB/Atherosclerosis AB/Arterial embolism and thrombosis AB/Phlebitis and thrombophlebitis AB/Other venous embolism and thrombosis AB/Varicose veins of lower extremities AB/Other disorders of veins AB/Hypotension AB/Pleural effusion, not elsewhere classified AB/Gastric ulcer AB/Duodenal ulcer AB/Inguinal hernia AB/Crohns disease [regional enteritis] AB/Diverticular disease of intestine AB/Other diseases of anus and rectum AB/Haemorrhoids and perianal venous thrombosis AB/Other diseases of liver AB/Cholelithiasis AB/Other diseases of biliary tract AB/Other diseases of digestive system AB/Cutaneous abscess, furuncle and carbuncle AB/Skin changes due to chronic exposure to nonionizing radiation AB/Decubitus ulcer and pressure area AB/Other soft tissue disorders, not elsewhere classified AB/Female genital prolapse AB/Other noninflammatory disorders of cervix uteri AB/Gestational [pregnancy-induced] hypertension AB/Obstructed labour due to maternal pelvic abnormality AB/Postpartum haemorrhage AB/Single spontaneous delivery AB/Single delivery by forceps and vacuum extractor AB/Pancreatic cancer AB/Non-melanoma cancer AB/Breast cancer AB/Corpus cancer 0.11058971029924898 0.11058971029924898 -0.09151498112135023 -0.13076828026902382 0.03342375548694973 -0.03621217265444472 0.08990511143939793 -0.03621217265444472 0.03342375548694973 0.03342375548694973 0.03342375548694973 -0.045757490560675115 0.02118929906993809 -0.045757490560675115 0.06818586174616162 0.041392685158225084 0.02118929906993809 0.01703333929878037 0.146128035678238 0.012837224705172215 0.01703333929878037 0.01703333929878037 0.02118929906993809 0.10380372095595687 0.1818435879447725 0.15836249209524966 0.02938377768520967 0.09342168516223506 0.02118929906993809 0.025305865264770258 -0.045757490560675115 -0.08092190762392612 -0.022276394711152253 0.05307844348341968 -0.03621217265444472 -0.022276394711152253 -0.07058107428570727 0.041392685158225084 0.02118929906993809 0.03742649794062367 -0.03151705144606486 0.02938377768520967 -0.02687214640030136 0.03742649794062367 0.012837224705172215 0.03742649794062367 0.05307844348341968 -0.02687214640030136 0.056904851336472564 -0.03151705144606486 -0.013228265733755159 0.02118929906993809 0.1367205671564068 -0.022276394711152253 0.03342375548694973 0.041392685158225084 2.6877934987111547 1.7290711630990636 5.064523889910164 1.9051929412874575 4.309257713478627 2.9105123090793263 13.295163964731534 1.9716201297063125 4.279826743603408 11.731381993876836 6.601945263855523 1.3602957291887148 1.893460303085612 1.646627295949384 2.543787439517037 1.8263796254258955 3.338515378434197 2.2267271449517367 91.34039082938023 2.6133637255796462 2.2315282130115284 2.169031366429599 2.9393760356362013 15.516893643413312 194.7583577161137 37.6237915623799 3.787169049076984 9.333626472157675 1.3602957291887148 1.5568054599362344 5.816125655674781 13.53681208532083 2.0239680844632497 2.581429574358396 8.038954292406912 1.7826866897590998 23.338382333194986 1.5092892152963218 2.2204791409111286 1.677550567507348 6.774873978991862 1.6259599743146365 4.790053366504275 1.5293452585595184 1.6454206859436251 6.137580944753443 3.0741328865335413 2.385736641072692 2.511985142432584 3.1920028992677523 1.5501129653773276 1.798968900525268 9.891216519459244 1.382902209418457 3.3778264770652053 2.5162630926603566 48.0/4940000.0 360.0/4940000.0 540.0/4940000.0 417.0/4940000.0 1557.0/4930000.0 1503.0/4940000.0 690.0/4940000.0 247.0/4940000.0 306.0/4940000.0 1059.0/4920000.0 10666.0/4880000.0 6381.0/4920000.0 5738.0/4920000.0 3864.0/4920000.0 1153.0/4930000.0 3613.0/4910000.0 4300.0/4910000.0 11994.0/4840000.0 31528.0/4730000.0 14839.0/4890000.0 2141.0/4930000.0 1564.0/4930000.0 10313.0/4860000.0 10353.0/4870000.0 88709.0/4350000.0 9949.0/4900000.0 4112.0/4920000.0 9286.0/4890000.0 42774.0/4710000.0 11478.0/4870000.0 5031.0/4930000.0 25834.0/4810000.0 20324.0/4860000.0 20772.0/4890000.0 5806.0/4920000.0 6291.0/4910000.0 3733.0/4930000.0 13718.0/4850000.0 3456.0/4920000.0 10644.0/4840000.0 2488.0/4930000.0 7142.0/4920000.0 7897.0/4900000.0 4994.0/4910000.0 14121.0/4810000.0 2627.0/4910000.0 16496.0/4830000.0 8648.0/4880000.0 10263.0/4860000.0 4543.0/4910000.0 16801.0/4870000.0 1036.0/4930000.0 3149.0/4910000.0 7955.0/4870000.0 16504.0/4830000.0 3993.0/4930000.0 5763.0/4920000.0 21258.0/4750000.0 48990.0/4600000.0 9074.0/4860000.0 11908.0/4820000.0 1222.0/4930000.0 7601.0/4870000.0 5261.0/4890000.0 1364.0/4930000.0 7499.0/4870000.0 1442.0/4930000.0 1472.0/4940000.0 7662.0/4880000.0 4561.0/4780000.0 <b>%{text}</b><br>FDR-P: %{hovertext:,.2g}:<br>IRR (95% CI): %{meta}<br>Events/Person-years: %{customdata}<extra></extra> 0.005841620160873623 0.009521558131860465 0.043621869162074015 0.000269569838759273 0.034444634348768814 0.00031805498017160384 0.02199031868218486 0.003207935046810969 0.004585046001436099 0.036426298619802684 3.8811515146896953e-7 0.021396673063626755 3.5403394975956703e-13 0.000011740993066566831 0.001149804395021431 0.00007584241762500356 0.000018807900785553426 0.000006412377538964349 2.7665043346354644e-10 2.746436944078697e-9 0.01495074830859509 0.00032306519788340247 0.021214890302167614 0.024703802908695328 0.000009278510196852166 3.7164389317130344e-100 0.005932979599856991 4.942894241399128e-9 0.0044093007011760145 0.03933214851512841 0.0332923512142974 0.00005250168674437825 0.001128395613232956 8.716902956323803e-8 0.0000023741265982994566 1.1053562295239563e-8 1.0702433779926795e-34 2.4718417577876734e-202 1.3168939252815545e-52 0.015886605072118587 3.050825746967659e-9 0.00047591196393217624 6.400123890420273e-7 1.8196372248450512e-16 3.843906381874529e-15 0.0033048757747934443 1.0947982905818722e-7 2.746436944078697e-9 1.624093233440522e-51 1.1413501671313972e-7 1.0142413797616617e-11 0.032637520283311565 0.034444634348768814 0.0018349487546347031 1.0390254615111552e-8 0.00004118592746399048 0.0006881475402255501 0.0005967978556983151 0.0071021128911487345 2.398788558131353e-7 9.796914559431159e-10 0.002297367774908658 0.023832101392905796 0.00010164950925085029 0.0052797790022068615 0.0007847240936749334 0.00022815776597178363 7.689555208650067e-12 0.00014951587572311096 0.04056531108480611 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 white 0 4.56 9.84 9.28 10.32 7.36 7.04 6.96 10.56 6.32 7.2 8.56 8.4 7.12 8.88 9.2 7.36 7.36 8.48 8.4 8.56 7.36 7.04 7.68 7.68 7.76 10.4 7.52 7.36 7.84 7.76 7.6 8.32 8.32 8.4 7.36 8.8 10.32 11.12 11.04 8.32 9.28 8.48 7.44 6.96 7.36 8.72 7.52 7.36 6.72 8.88 7.44 8.88 8.64 8.48 7.52 8.8 8.56 7.68 8.16 7.44 8.64 8.72 8.24 7.52 7.52 8.4 7.36 10.32 7.52 8.4 0.57(0.42-0.77) 1.23(1.1-1.39) 1.16(1.05-1.27) 1.29(1.15-1.44) 0.92(0.87-0.97) 0.88(0.83-0.93) 0.87(0.8-0.95) 1.32(1.15-1.53) 0.79(0.7-0.9) 0.9(0.84-0.96) 1.07(1.05-1.09) 1.05(1.02-1.08) 0.89(0.86-0.91) 1.11(1.06-1.15) 1.15(1.08-1.23) 0.92(0.88-0.95) 0.92(0.89-0.95) 1.06(1.04-1.09) 1.05(1.04-1.07) 1.07(1.05-1.09) 0.92(0.87-0.96) 0.88(0.83-0.93) 0.96(0.94-0.98) 0.96(0.94-0.99) 0.97(0.96-0.98) 1.3(1.27-1.33) 0.94(0.91-0.97) 0.92(0.9-0.94) 0.98(0.96-0.99) 0.97(0.95-0.99) 0.95(0.92-0.98) 1.04(1.02-1.06) 1.04(1.02-1.05) 1.05(1.03-1.07) 0.92(0.9-0.95) 1.1(1.07-1.14) 1.29(1.24-1.34) 1.39(1.36-1.42) 1.38(1.33-1.44) 1.04(1.02-1.06) 1.16(1.11-1.22) 1.06(1.03-1.09) 0.93(0.91-0.95) 0.87(0.84-0.9) 0.92(0.9-0.94) 1.09(1.04-1.14) 0.94(0.93-0.96) 0.92(0.9-0.95) 0.84(0.82-0.86) 1.11(1.07-1.14) 0.93(0.92-0.95) 1.11(1.04-1.18) 1.08(1.03-1.13) 1.06(1.03-1.09) 0.94(0.92-0.96) 1.1(1.06-1.15) 1.07(1.04-1.1) 0.96(0.94-0.98) 1.02(1.01-1.04) 0.93(0.91-0.95) 1.08(1.05-1.1) 1.09(1.04-1.14) 1.03(1.01-1.04) 0.94(0.92-0.97) 0.94(0.91-0.97) 1.05(1.02-1.07) 0.92(0.88-0.95) 1.29(1.2-1.38) 0.94(0.92-0.97) 1.05(1.02-1.08) markers B 0.5 B/Hereditary factor VIII deficiency B/Disorders of porphyrin and bilirubin metabolism B/Other disorders of middle ear and mastoid B/Portal vein thrombosis B/Pneumonia due to Streptococcus pneumoniae B/Peptic ulcer, site unspecified B/Femoral hernia B/Erythema nodosum B/Thyroid Well-diff  cancer B/Other endocrine  cancer B/Erysipelas B/Streptococcus and Staphylococcus as the cause of diseases classified B/Acute posthaemorrhagic anaemia B/Other coagulation defects B/Sarcoidosis B/Other nontoxic goitre B/Thyrotoxicosis [hyperthyroidism] B/Type 1 diabetes mellitus B/Type 2 diabetes mellitus B/Unspecified diabetes mellitus B/Hyperparathyroidism and other disorders of parathyroid gland B/Postprocedural endocrine and metabolic disorders, not elsewhere classified B/Sleep disorders B/Other disorders of external ear B/Essential (primary) hypertension B/Pulmonary embolism B/Nonrheumatic mitral valve disorders B/Nonrheumatic aortic valve disorders B/Atrial fibrillation and flutter B/Other cardiac arrhythmias B/Intracerebral haemorrhage B/Cerebral infarction B/Sequelae of cerebrovascular disease B/Atherosclerosis B/Aortic aneurysm and dissection B/Other peripheral vascular diseases B/Arterial embolism and thrombosis B/Phlebitis and thrombophlebitis B/Other venous embolism and thrombosis B/Varicose veins of lower extremities B/Other disorders of veins B/Pleural effusion, not elsewhere classified B/Gastric ulcer B/Duodenal ulcer B/Inguinal hernia B/Crohns disease [regional enteritis] B/Diverticular disease of intestine B/Other diseases of anus and rectum B/Haemorrhoids and perianal venous thrombosis B/Acute pancreatitis B/Other diseases of digestive system B/Pilonidal cyst B/Atopic dermatitis B/Psoriasis B/Skin changes due to chronic exposure to nonionizing radiation B/Decubitus ulcer and pressure area B/Ulcer of lower limb, not elsewhere classified B/Gonarthrosis [arthrosis of knee] B/Other soft tissue disorders, not elsewhere classified B/Calculus of kidney and ureter B/Female genital prolapse B/Other noninflammatory disorders of cervix uteri B/Labour and delivery complicated by fetal stress [distress] B/Postpartum haemorrhage B/Retained placenta and membranes, without haemorrhage B/Single delivery by forceps and vacuum extractor B/Puerperal sepsis B/Pancreatic cancer B/Non-melanoma cancer B/Cervix cancer -0.24412514432750865 0.08990511143939793 0.06445798922691845 0.11058971029924898 -0.03621217265444472 -0.05551732784983137 -0.060480747381381476 0.12057393120584987 -0.10237290870955856 -0.045757490560675115 0.02938377768520967 0.02118929906993809 -0.050609993355087216 0.04532297878665748 0.06069784035361165 -0.03621217265444472 -0.03621217265444472 0.025305865264770258 0.02118929906993809 0.02938377768520967 -0.03621217265444472 -0.05551732784983137 -0.017728766960431602 -0.017728766960431602 -0.013228265733755159 0.1139433523068368 -0.02687214640030136 -0.03621217265444472 -0.00877392430750515 -0.013228265733755159 -0.022276394711152253 0.01703333929878037 0.01703333929878037 0.02118929906993809 -0.03621217265444472 0.041392685158225084 0.11058971029924898 0.14301480025409505 0.13987908640123647 0.01703333929878037 0.06445798922691845 0.025305865264770258 -0.03151705144606486 -0.060480747381381476 -0.03621217265444472 0.03742649794062367 -0.02687214640030136 -0.03621217265444472 -0.07572071393811836 0.04532297878665748 -0.03151705144606486 0.04532297878665748 0.03342375548694973 0.025305865264770258 -0.02687214640030136 0.041392685158225084 0.02938377768520967 -0.017728766960431602 0.008600171761917571 -0.03151705144606486 0.03342375548694973 0.03742649794062367 0.012837224705172215 -0.02687214640030136 -0.02687214640030136 0.02118929906993809 -0.03621217265444472 0.11058971029924898 -0.02687214640030136 0.02118929906993809 2.2334666855342657 2.021291976752229 1.3602957291887148 3.5693287011321964 1.4628784211935837 3.4974977997601004 1.657768476827863 2.4937744337473373 2.3386563027268634 1.4385849564183402 6.411039402684041 1.66965374919441 12.450955089707888 4.9302951684129015 2.9393760356362013 4.1200878314655665 4.725659674844427 5.192980915784201 9.558068644984695 8.561230367570362 1.8253370696699571 3.4907098237256657 1.6733592095389611 1.6072361862086508 5.032521750637524 99.42987299910156 2.2267271449517367 8.306018681642831 2.3556302825734683 1.4052523296446862 1.4776555324691394 4.279826743603408 2.9475386108828747 7.0596377889079545 5.624496126376818 7.956497736834558 33.9705174506323 201.60697933533046 51.880449205691356 1.798968900525268 8.515582597107372 3.3224733773520807 6.193811619077812 15.740015187263365 14.415227198092568 2.480844860334366 6.960665889368818 8.561230367570362 50.78938904307114 6.942581093248693 10.993858674762757 1.4862828452669676 1.4628784211935837 2.7363760599623763 7.9833738098458 4.385251149712882 3.162318438165183 3.2241727459577434 2.148612428681364 6.620008031350127 9.008910679491114 2.6387694750583015 1.6228376620972331 3.992894713731916 2.277384255521252 3.105283012881487 3.6417647442426606 11.114098780616722 3.8253126911329582 1.391845189182081 7138.0/41890000.0 38978.0/41730000.0 103140.0/40990000.0 134002.0/40770000.0 51770.0/41460000.0 767088.0/36750000.0 85181.0/41420000.0 169903.0/40220000.0 63991.0/41470000.0 18635.0/41690000.0 19846.0/41730000.0 44800.0/41470000.0 <b>%{text}</b><br>FDR-P: %{hovertext:,.2g}:<br>IRR (95% CI): %{meta}<br>Events/Person-years: %{customdata}<extra></extra> 0.02539737411576572 0.03143699766957893 0.0007606242022195508 0.003889790666440278 0.02212921831160521 0.006453314372260607 0.04049927688611511 0.0023799138526947572 0.00003858355628976596 0.02306833453717046 3.321938819006852e-7 0.03143699766957893 orange orange orange orange orange orange orange orange orange orange orange orange white 0 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 7.2 8.4 8.32 8.32 8.4 8.16 7.76 8.24 8.48 8.64 8.48 7.76 0.9(0.85-0.95) 1.05(1.02-1.08) 1.04(1.02-1.06) 1.04(1.02-1.05) 1.05(1.02-1.07) 1.02(1.01-1.03) 0.97(0.95-0.99) 1.03(1.02-1.05) 1.06(1.04-1.08) 1.08(1.04-1.13) 1.06(1.04-1.08) 0.97(0.95-0.98) markers RhD positive 0.5 RhD/Disseminated intravascular coagulation [defibrination syndrome] RhD/Chorioretinal disorders in diseases classified elsewhere RhD/Other rheumatic heart diseases RhD/Chronic sinusitis RhD/Chronic laryngitis and laryngotracheitis RhD/Bronchitis, not specified as acute or chronic RhD/Airway disease due to specific organic dust RhD/Exfoliative dermatitis RhD/Reactive arthropathies RhD/Unspecified contracted kidney RhD/Other disorders of male genital organs RhD/Pre-eclampsia superimposed on chronic hypertension -0.045757490560675115 0.02118929906993809 0.01703333929878037 0.01703333929878037 0.02118929906993809 0.008600171761917571 -0.013228265733755159 0.012837224705172215 0.025305865264770258 0.03342375548694973 0.025305865264770258 -0.013228265733755159 1.5952111836157112 1.502558937117228 3.1188298599352478 2.410073770102595 1.6550339267393608 2.1902171777857204 1.3925527310365318 2.6234387631016505 4.413597745436532 1.6369837590734502 6.478608370323036 1.502558937117228 lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey 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0.018643737484970217 0.6279464427896482 0.005481540917638052 0.00009183918491971155 0.021213610432147385 0.09507501245045036 0.10521184528502744 0.021162470969322663 0.12424163050456903 0.2236349436422875 3196.0/10110000.0 368.0/1150000.0 691.0/2400000.0 3785.0/10100000.0 412.0/1150000.0 18682.0/10000000.0 2205.0/1140000.0 4443.0/2380000.0 4019.0/10100000.0 22398.0/9970000.0 17731.0/10010000.0 6294.0/10100000.0 885.0/1150000.0 1580.0/2400000.0 12890.0/10070000.0 7070.0/10090000.0 3487.0/10110000.0 1229.0/10120000.0 158.0/1150000.0 300.0/2400000.0 11346.0/10050000.0 1508.0/1140000.0 2808.0/2390000.0 294.0/10130000.0 2414.0/10110000.0 314.0/1150000.0 624.0/2400000.0 12235.0/10010000.0 1453.0/1140000.0 1701.0/10120000.0 217.0/1150000.0 3802.0/10100000.0 2500.0/10110000.0 579.0/2400000.0 18660.0/9960000.0 4285.0/2370000.0 13245.0/10040000.0 16193.0/10000000.0 1629.0/1140000.0 3470.0/2380000.0 19179.0/9940000.0 2248.0/1130000.0 63099.0/9670000.0 2827.0/2380000.0 3325.0/10100000.0 335.0/1150000.0 10000.0/10010000.0 1116.0/1140000.0 1049.0/10130000.0 6245.0/18270000.0 <b>%{text}</b><br>P-value: %{hovertext:,.2g}:<br>IRR: %{marker.size:,.2f}<br>IRR (95% CI): %{meta}<br>Events/Person-years: %{customdata}<extra></extra> 5.9279517326615935e-27 2.2741366177265873e-7 0.00003966658310910288 4.4274659627665216e-8 0.0000813134024224098 2.3379481446869263e-15 0.00005268583773887552 0.000035467715424940147 0.00003489044125011719 7.069606478292024e-29 7.393736741385009e-10 1.4009832564529781e-100 2.8611074052158293e-63 9.921887924740507e-59 0.00001552735501569423 0.00008253371142307604 0.000007910617636681671 1.2318896130774206e-12 0.000004374012214034502 0.0000012149865650518974 3.5585256329358354e-172 2.4679068084979954e-90 6.889014903151835e-96 0.000021694176625131715 4.187283884320474e-32 2.7776444502766993e-16 1.173627378975445e-22 3.9071035051585974e-15 0.000003764592841490944 1.612912427942609e-10 0.000006732117882065603 0.000024800375690705287 1.0000696564521117e-9 0.000001276348075394313 3.5391720326690884e-11 2.14351872188057e-8 1.3330223552682052e-16 1.7019627417696667e-9 3.132944756582289e-11 9.693850079521083e-17 4.8295194180712515e-12 0.00002300098794704263 1.3800452312532788e-7 0.00000923015815631539 0.0000029375678645042996 5.348023366727523e-7 9.732135854616949e-12 6.068482637462496e-7 0.000017167797899860627 7.776980945070983e-15 black white 0 0.8 6.5 6.45 5.85 4.5 4.2 5.4 5.45 5.3500000000000005 5.5 5.5 5.3500000000000005 7.8500000000000005 9.45 8.2 5.25 5.3500000000000005 5.6000000000000005 6.949999999999999 7.45 6.949999999999999 7.800000000000001 8.95 8.05 7.55 7.45 8.35 8 5.5 5.6000000000000005 6.2 6.75 4.6000000000000005 4.3 4.1499999999999995 4.699999999999999 4.6000000000000005 4.55 4.6000000000000005 4.050000000000001 4.1499999999999995 5.3500000000000005 5.45 5.15 4.65 4.75 4.35 5.2 5.3500000000000005 6.8999999999999995 5.6000000000000005 1.3(1.24-1.37) 1.29(1.17-1.42) 1.17(1.09-1.26) 0.9(0.86-0.93) 0.84(0.77-0.92) 1.08(1.06-1.1) 1.09(1.04-1.13) 1.07(1.03-1.1) 1.1(1.05-1.15) 1.1(1.08-1.12) 1.07(1.05-1.09) 1.57(1.51-1.64) 1.89(1.75-2.03) 1.64(1.54-1.74) 1.05(1.03-1.08) 1.07(1.03-1.1) 1.12(1.07-1.18) 1.39(1.27-1.52) 1.49(1.26-1.77) 1.39(1.22-1.59) 1.56(1.51-1.61) 1.79(1.69-1.89) 1.61(1.54-1.68) 1.51(1.25-1.83) 1.49(1.39-1.59) 1.67(1.48-1.89) 1.6(1.46-1.76) 1.1(1.07-1.12) 1.12(1.07-1.18) 1.24(1.16-1.33) 1.35(1.18-1.54) 0.92(0.88-0.95) 0.86(0.82-0.9) 0.83(0.76-0.89) 0.94(0.92-0.96) 0.92(0.89-0.95) 0.91(0.89-0.93) 0.92(0.9-0.95) 0.81(0.76-0.86) 0.83(0.79-0.87) 1.07(1.05-1.09) 1.09(1.05-1.13) 1.03(1.02-1.05) 0.93(0.89-0.96) 0.95(0.92-0.97) 0.87(0.83-0.92) 1.04(1.03-1.06) 1.07(1.04-1.1) 1.38(1.19-1.59) 1.12(1.09-1.16) markers Concordant between Main and Donor cohort, ABO and RhD 0.8 A/Other coagulation defects AB/Other coagulation defects B/Other coagulation defects A/Thyrotoxicosis [hyperthyroidism] AB/Thyrotoxicosis [hyperthyroidism] A/Type 2 diabetes mellitus AB/Type 2 diabetes mellitus B/Type 2 diabetes mellitus A/Unspecified diabetes mellitus A/Disorders of lipoprotein metabolism and other lipidaemias A/Chronic ischaemic heart disease A/Pulmonary embolism AB/Pulmonary embolism B/Pulmonary embolism A/Heart failure A/Sequelae of cerebrovascular disease A/Atherosclerosis A/Arterial embolism and thrombosis AB/Arterial embolism and thrombosis B/Arterial embolism and thrombosis A/Phlebitis and thrombophlebitis AB/Phlebitis and thrombophlebitis B/Phlebitis and thrombophlebitis A/Portal vein thrombosis A/Other venous embolism and thrombosis AB/Other venous embolism and thrombosis B/Other venous embolism and thrombosis A/Varicose veins of lower extremities AB/Varicose veins of lower extremities A/Other disorders of veins AB/Other disorders of veins A/Gastric ulcer A/Duodenal ulcer B/Duodenal ulcer A/Inguinal hernia B/Inguinal hernia A/Diverticular disease of intestine A/Haemorrhoids and perianal venous thrombosis AB/Haemorrhoids and perianal venous thrombosis B/Haemorrhoids and perianal venous thrombosis A/Cholelithiasis AB/Cholelithiasis A/Other soft tissue disorders, not elsewhere classified B/Calculus of kidney and ureter A/Gestational [pregnancy-induced] hypertension AB/Gestational [pregnancy-induced] hypertension A/Single delivery by forceps and vacuum extractor AB/Single delivery by forceps and vacuum extractor A/Pancreatic cancer pos/Gestational [pregnancy-induced] hypertension 0.1139433523068368 0.11058971029924898 0.06818586174616162 -0.045757490560675115 -0.07572071393811836 0.03342375548694973 0.03742649794062367 0.02938377768520967 0.041392685158225084 0.041392685158225084 0.02938377768520967 0.19589965240923374 0.2764618041732441 0.21484384804769785 0.02118929906993809 0.02938377768520967 0.04921802267018165 0.14301480025409505 0.17318626841227402 0.14301480025409505 0.1931245983544616 0.2528530309798932 0.20682587603184974 0.17897694729316946 0.17318626841227402 0.22271647114758325 0.2041199826559248 0.041392685158225084 0.04921802267018165 0.09342168516223506 0.13033376849500616 -0.03621217265444472 -0.06550154875643227 -0.08092190762392612 -0.02687214640030136 -0.03621217265444472 -0.040958607678906384 -0.03621217265444472 -0.09151498112135023 -0.08092190762392612 0.02938377768520967 0.03742649794062367 0.012837224705172215 -0.03151705144606486 -0.022276394711152253 -0.060480747381381476 0.01703333929878037 0.02938377768520967 0.13987908640123647 0.04921802267018165 24.49202899149897 5.416272587595753 3.3843642069785678 6.095899673906062 3.0930297700616123 13.08798430220359 3.2702384882470312 3.423615757311153 3.423615757311153 26.364385887913407 7.802890998383454 97.46528819159971 60.55312698380104 56.09224807421816 3.7216536494262114 3.0930297700616123 3.9922643442950236 10.424239330135073 4.226113650212195 4.731269643530338 168.75942104237214 87.52042237608107 92.94965527132445 3.597597259590687 29.53385677523837 13.980957839674065 20.241160908480772 12.894927483428596 4.279041173150952 8.425299647324708 4.050741152903644 3.5596855575377875 7.690872132228758 4.723235952914101 9.062819463130584 6.394537207777352 14.265034954173153 7.4776811009801945 9.093492004822703 14.365587527188012 9.857236145677863 3.5824131060586204 5.617955851497222 3.936546605292288 4.374182149331852 5.059619099470821 9.577755483195354 5.018972720992252 3.6887604054795946 12.19273501658916 helvetica 900 white helvetica 18 constant white black dot 0.5 1 -0.8 0.8 1.3010299956639813 1.3010299956639813 true #2a3f5f #2a3f5f #E5ECF6 0.5 #E5ECF6 0.5 #2a3f5f white white white #2a3f5f #2a3f5f white white white #2a3f5f 0  0  0 #0d0887 0.1111111111111111 #46039f 0.2222222222222222 #7201a8 0.3333333333333333 #9c179e 0.4444444444444444 #bd3786 0.5555555555555556 #d8576b 0.6666666666666666 #ed7953 0.7777777777777778 #fb9f3a 0.8888888888888888 #fdca26 1 #f0f921 0  0  0 #0d0887 0.1111111111111111 #46039f 0.2222222222222222 #7201a8 0.3333333333333333 #9c179e 0.4444444444444444 #bd3786 0.5555555555555556 #d8576b 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#E5ECF6 white 2 white true  white #2a3f5f white white  white white  #E5ECF6 white white  0.05 true white white  15 white 2 true white white  15 white 2 #333333 14 <b>Volcanoplot showing Incidence Rate Ratios/False Discovery Rate Adjusted P-Values Depending On ABO Blood Group and RhD Status<br> 1200 white black -0.8 0.8 false true -0.5 0 0.5 <b>IRR true black 1 -5 140 false true 5 outside FDR-P 0.05 50 100 1.3010299956639813 50 100 1 <b>-log10(FDR-adjusted p-value) truedf = pd.read_csv('df_man.csv')
df_r = pd.read_csv('df_r_man.csv')
concordant = pd.read_csv('concordant_man.csv')
mchap = pd.read_csv('mchap.csv')

fig = go.Figure()
fdr_p=df['fdr_p']

grp=df['bg'].unique().tolist()
for groups in grp:
        data_filtered=df[(df.bg==groups) & (df.fdr_p < 0.05)]
        fig.add_trace(go.Scatter(x=data_filtered['row'], 
                         y=data_filtered['y'], 
                         mode='markers',
                             opacity=0.5,
                         marker=dict(color=data_filtered['color'],line=dict(color='white',width=0)),
                         text=data_filtered['bg_cat'],
                         customdata=data_filtered['event_pyrs'],
                         hovertext=data_filtered['fdr_p'],
                     
                        meta=data_filtered['combined'],
                        hovertemplate = "<b>%{text}</b>" +
                         "<br>FDR-P: %{hovertext:,.2g}:" +
                         "<br>IRR (95% CI): %{meta}" +
                         "<br>Events/Person-years: %{customdata}" +
                         "<extra></extra>",
                         marker_size=(9*data_filtered['irr']),
                         name=groups
                        )
              )



df_r2=df_r[df_r.fdr_p<0.05]
fig.add_trace(go.Scatter(x=df_r2['x'], 
                         y=df_r2['y'], 
                         mode='markers',
                             opacity=0.5,
                         marker=dict(color=df_r2['color'],opacity=df_r2['opacity'],line=dict(color='white',width=0)),
                         text=df_r2['bg_cat'],
                         customdata=df_r2['event_pyrs'],
                         hovertext=df_r2['fdr_p'],
                        meta=df_r2['combined'],
                        hovertemplate = "<b>%{text}</b>" +
                         "<br>FDR-P: %{hovertext:,.2g}:" +
                         "<br>IRR (95% CI): %{meta}" +
                         "<br>Events/Person-years: %{customdata}" +
                         "<extra></extra>",
                         name='RhD positive'
                        )
              )
              
fig.add_trace(go.Scatter(x=pd.concat([df_r.x[(df_r.fdr_p>=0.05)],df.x[(df.fdr_p>=0.05)]]), 
                         y=pd.concat([df_r.y[(df_r.fdr_p>=0.05)],df.y[(df.fdr_p>=0.05)]]), 
                         mode='markers',
                             opacity=0.7,
                         marker=dict(color=pd.concat([df_r.color[(df_r.fdr_p>=0.05)],df.color[(df.fdr_p>=0.05)]]),opacity=0.7,line=dict(color='white',width=0)),

                         marker_size=2,
                         name='Non-significant ABO and RhD',
                         showlegend=True,
                        )
              )
    
    


fig.add_trace(go.Scatter(x=concordant.x, 
                         y=concordant.y, 
                         mode='markers',
                             opacity=0.8,
                         marker=dict(color=concordant['color'],opacity=0.8,line=dict(color='white',width=0)),
                         text=concordant['bg_cat'],
                        customdata=concordant['event_pyrs'],
                         hovertext=concordant['bon_p'],
                        meta=concordant['combined'],
                        hovertemplate = "<b>%{text}</b>" +
                         "<br>BON-P: %{hovertext:,.2g}:" +
                         "<br>IRR (95% CI): %{meta}" +
                         "<br>Events/Person-years: %{customdata}" +
                         "<extra></extra>",
                         marker_size=(5*concordant['irr']),
                         name='Concordant in validation cohort, after bonferroni-adjustment'
                        )
              )

fig.add_trace(go.Scatter(x=[], 
                         y=[],
                        mode='markers',
                         xaxis='x2'
                        )
             )

fig.add_shape(
       # Line Horizontal
          type="line",
         x0=0,
        x1=df.x.max()+1,
        y0=-(np.log10(0.05)),
        y1=-(np.log10(0.05)),
           line=dict(
              color="black",
             width=0.5,
            dash="dot"
       ), opacity=1,
)

    
#Layout
fig.update_layout(
    title='<b>Manhattanplot - Disease catagories/False Discovery Rate Adjusted P-Values In Main Cohort Depending On ABO Blood Group. </b> <br>'
                  ''
                  '',
                  title_font_color = '#333333',
                  title_font_size = 14,
                  
                  font=dict(family="helvetica"),
                  
                  xaxis=dict(
                      anchor='y',
                      title='<b>',
                      visible=True,
                      showline=True,
                      gridcolor='white',
                      tickangle = 300,
                      range=[0,df.x.max()],
                      showgrid=False,
                      ticks=('inside'),
                      ticklen=0,
                     # tickangle=0,
                      tickvals=mchap['median'],
                      ticktext=mchap['names'].tolist(),
                      linecolor='black',
                      linewidth=1),

                  xaxis2=dict(
                      anchor='y',
                      overlaying='x',
                      title='<b>',
                      visible=True,
                      showline=True,
                      gridcolor='white',
                      tickangle = 0,
                      range=[0,df.x.max()],
                      showgrid=False,
                      ticklen=5,
                      tickvals=mchap['mins'],
                      showticklabels=False,
                   #   ticktext=["","","","","","","","","","","","","","","","","","","","","","","","","","","","","","","","","","","","","","","","",],
                      linecolor='black',
                      tickcolor='black',
                      ticks=('outside'),
                      linewidth=1),

                  plot_bgcolor='white',
                  showlegend=True,
                  legend= {'itemsizing': 'constant'},
                  hoverlabel=dict(
                        bgcolor="white", 
                        font_size=18, 
                        font_family="helvetica"),
                  
                  yaxis_ticks=('outside'),
                  yaxis_tickwidth=1,
                  yaxis_ticklen=5,
                  yaxis_title='<b>-log10(FDR-adjusted p-value)',
                  yaxis_showline=True,
                  yaxis_showgrid=False,
                  yaxis_visible=True,
                  yaxis_linewidth=1,
                  yaxis_linecolor='black',
                  #yaxis_range=[-5,190],
                  #yaxis_tickangle = 90,
                  yaxis_tickvals=[-(np.log10(0.05)),50, 100],
                  yaxis_ticktext=['P 0.05',50,100],
                               #yaxis_ticksuffix='%',
                  yaxis_range=[-0.5,130],
                  
                  width=1500,
                  height=1200
                  )

    

fig.show() python 6 application/vnd.plotly.v1+json https://plot.ly 110.0/23680000.0 2575.0/23650000.0 1857.0/23670000.0 6979.0/23640000.0 3498.0/23650000.0 10391.0/23660000.0 315.0/23680000.0 16529.0/23520000.0 5235.0/23580000.0 17105.0/23580000.0 44766.0/23370000.0 50400.0/23370000.0 1103.0/23680000.0 28811.0/23530000.0 119781.0/23250000.0 19188.0/23570000.0 18124.0/23520000.0 20884.0/23500000.0 5425.0/23630000.0 56909.0/23190000.0 153031.0/22630000.0 70329.0/23450000.0 9782.0/23630000.0 10345.0/23600000.0 123807.0/22700000.0 11052.0/23630000.0 27973.0/23620000.0 284515.0/21700000.0 134179.0/22810000.0 30868.0/23420000.0 30777.0/23420000.0 15003.0/23500000.0 14747.0/23510000.0 6899.0/23610000.0 3083.0/23650000.0 76086.0/23040000.0 2707.0/23650000.0 431328.0/20810000.0 150234.0/22380000.0 160247.0/22890000.0 222693.0/22620000.0 47762.0/23460000.0 9522.0/23650000.0 21801.0/23550000.0 49161.0/23400000.0 50993.0/23660000.0 212239.0/22500000.0 256960.0/22840000.0 24107.0/23590000.0 122308.0/23050000.0 97713.0/23420000.0 29265.0/23520000.0 16275.0/23610000.0 65116.0/23250000.0 16090.0/23580000.0 53057.0/23170000.0 11887.0/23620000.0 38694.0/23520000.0 14564.0/23490000.0 2201.0/23670000.0 191345.0/23010000.0 17016.0/23350000.0 86889.0/23270000.0 75624.0/23010000.0 10598.0/23640000.0 34049.0/23550000.0 21119.0/23540000.0 20750.0/23540000.0 37253.0/23470000.0 23213.0/23540000.0 71181.0/23130000.0 69977.0/23000000.0 43716.0/23450000.0 78557.0/23120000.0 42718.0/23380000.0 54485.0/23220000.0 9899.0/23650000.0 96699.0/22720000.0 8733.0/23580000.0 80122.0/23300000.0 7576.0/23620000.0 80234.0/23140000.0 28362.0/23550000.0 4285.0/23650000.0 77812.0/22940000.0 5440.0/23630000.0 66162.0/23290000.0 28484.0/23410000.0 150878.0/22530000.0 234444.0/22020000.0 45350.0/23260000.0 10336.0/23610000.0 15715.0/23560000.0 10318.0/23600000.0 10780.0/23590000.0 2122.0/23660000.0 24915.0/23440000.0 230445.0/21120000.0 60221.0/23060000.0 12890.0/23580000.0 291.0/23680000.0 2096.0/23660000.0 7590.0/23670000.0 28721.0/23450000.0 37292.0/23380000.0 35680.0/23050000.0 21466.0/22890000.0 8696.0/23530000.0 7359.0/23590000.0 9589.0/23660000.0 <b>%{text}</b><br>FDR-P: %{hovertext:,.2g}:<br>IRR (95% CI): %{meta}<br>Events/Person-years: %{customdata}<extra></extra> 0.02293802559719567 0.00013941181374085105 0.00007300984608716175 1.8196372248450512e-16 0.022056113577998117 0.0252347621063933 0.0042506638207039 0.0004586534045232676 0.003337416375269762 3.8410250306581805e-12 0.007792966407587427 7.669771134145466e-12 0.011299396621767724 6.879062643844708e-12 2.4622538258750725e-8 5.788271064730156e-28 0.000875530669332288 4.4416754998274993e-11 0.0497253763285969 2.996631282347816e-11 9.800789646031263e-42 1.6961649922784994e-19 0.033882939676894125 0.00000658870869538009 1.883335223660511e-39 0.003207935046810969 0.01671935731967564 0.02534022173708447 9.305491592398458e-11 0.007404380098461815 0.014786978703750097 0.004049992634876436 4.2300827769346224e-9 0.043542679886250366 8.897313033448127e-8 0.005493682538471979 0.0029134796537462057 0.0052797790022068615 0.000029272002870943487 3.442053690687893e-13 5.0202312762138365e-17 1.1372602582170523e-248 0.003207935046810969 0.002093449845713228 0.0340605008621709 0.00046484003068619035 4.055765782985835e-7 3.8348670868343234e-30 0.000058126101851453736 1.0581902267803034e-8 2.387359447858513e-13 4.4416754998274993e-11 2.5679870844074596e-34 9.999999999999996e-241 2.1365502398129545e-103 1.5044877692967665e-24 1.365764584022765e-22 0.000008619381634322138 0.015927797189729153 9.999999999999996e-241 0.0063365970762997844 7.994897672217332e-8 0.005720375901451594 0.0006285693980926897 0.003797092682659868 7.1620523468966574e-9 0.000018807900785553426 0.029251956314578175 8.054377817684128e-27 4.6724725582495644e-67 0.039288069654177804 6.584986589339964e-16 0.01584313577849722 1.0107348631579524e-29 2.4006509284691933e-10 4.163396727465196e-27 0.002406234994412123 0.000010762118259698724 0.01023360260614935 5.0447789052433664e-33 0.02200486366390021 2.5252517858055945e-16 0.0003171304023346398 0.01969959211754981 0.0000051009266594339544 0.00003006620886374865 0.007222077945545772 0.016061333260174226 0.04131845993467484 0.000012969645820574765 0.00033546538874346164 0.011299396621767724 0.02195297813929367 0.034444634348768814 2.639758000079009e-14 0.0003472664640193846 4.477296530327382e-11 0.0001324901052159423 9.999999999999996e-241 0.0036001979934406733 0.035026276376422416 0.0005818505604396704 6.950274775414566e-49 0.00005946172815666035 0.00000973781831723126 6.809097304486495e-10 0.002841471735951429 0.00018264736732168514 0.00039689319810017797 0.021620813767578653 #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f #2f4f4f white 0 15.48 10.35 10.709999999999999 7.74 8.280000000000001 9.450000000000001 12.78 9.450000000000001 8.370000000000001 8.19 8.73 9.540000000000001 8.19 8.459999999999999 9.27 10.35 8.64 8.370000000000001 8.459999999999999 9.540000000000001 9.63 9.540000000000001 9.450000000000001 8.280000000000001 9.72 8.549999999999999 8.73 9.09 9.36 9.36 9.27 9.450000000000001 9.81 9.540000000000001 10.709999999999999 9.18 10.169999999999998 8.91 9.27 9.36 9.36 11.790000000000001 9.63 9.36 9.18 9.27 9.18 9.36 8.549999999999999 9.27 9.36 9.63 10.62 12.419999999999998 12.06 9.72 10.44 9.36 9.450000000000001 8.73 9.09 9.72 9.18 9.27 9.540000000000001 9.540000000000001 8.549999999999999 8.73 8.280000000000001 7.56 8.82 8.549999999999999 8.82 8.370000000000001 8.549999999999999 8.370000000000001 9.540000000000001 9.27 9.540000000000001 8.370000000000001 9.540000000000001 8.549999999999999 8.64 8.370000000000001 8.73 9.99 9.18 9.27 9.09 9.18 8.73 8.459999999999999 8.64 8.549999999999999 8.459999999999999 8.459999999999999 8.549999999999999 8.82 9.09 9.27 6.93 7.83 12.419999999999998 8.64 8.64 9.540000000000001 9.36 9.450000000000001 9.540000000000001 9.450000000000001 1.72(1.23-2.39) 1.15(1.08-1.22) 1.19(1.11-1.28) 0.86(0.83-0.89) 0.92(0.88-0.97) 1.05(1.02-1.08) 1.42(1.18-1.71) 1.05(1.03-1.08) 0.93(0.89-0.96) 0.91(0.89-0.94) 0.97(0.96-0.99) 1.06(1.04-1.07) 0.91(0.86-0.96) 0.94(0.92-0.95) 1.03(1.02-1.04) 1.15(1.12-1.18) 0.96(0.94-0.98) 0.93(0.91-0.95) 0.94(0.91-0.98) 1.06(1.04-1.07) 1.07(1.06-1.08) 1.06(1.05-1.07) 1.05(1.02-1.08) 0.92(0.89-0.95) 1.08(1.07-1.1) 0.95(0.92-0.97) 0.97(0.95-0.99) 1.01(1.0-1.02) 1.04(1.03-1.05) 1.04(1.02-1.06) 1.03(1.01-1.05) 1.05(1.02-1.08) 1.09(1.06-1.12) 1.06(1.02-1.1) 1.19(1.12-1.25) 1.02(1.01-1.04) 1.13(1.06-1.2) 0.99(0.98-0.99) 1.03(1.02-1.04) 1.04(1.03-1.05) 1.04(1.03-1.05) 1.31(1.29-1.33) 1.07(1.03-1.1) 1.04(1.02-1.06) 1.02(1.01-1.04) 1.03(1.02-1.04) 1.02(1.01-1.03) 1.04(1.04-1.05) 0.95(0.93-0.97) 1.03(1.02-1.04) 1.04(1.03-1.05) 1.07(1.05-1.09) 1.18(1.15-1.21) 1.38(1.36-1.4) 1.34(1.31-1.38) 1.08(1.06-1.09) 1.16(1.13-1.2) 1.04(1.02-1.06) 1.05(1.02-1.08) 0.97(nan-nan) 1.01(1.01-1.02) 1.08(1.05-1.1) 1.02(1.01-1.03) 1.03(1.01-1.04) 1.06(1.03-1.09) 1.06(1.04-1.07) 0.95(0.93-0.97) 0.97(0.95-0.99) 0.92(0.9-0.93) 0.84(0.83-0.86) 0.98(0.97-0.99) 0.95(0.94-0.96) 0.98(0.96-0.99) 0.93(0.92-0.94) 0.95(0.94-0.96) 0.93(0.92-0.94) 1.06(1.03-1.1) 1.03(1.02-1.04) 1.06(1.03-1.1) 0.93(0.92-0.94) 1.06(1.02-1.09) 0.95(0.94-0.96) 0.96(0.94-0.98) 0.93(0.89-0.97) 0.97(0.96-0.98) 1.11(1.06-1.15) 1.02(1.01-1.04) 1.03(1.01-1.05) 1.01(1.0-1.02) 1.02(1.01-1.03) 0.97(0.95-0.98) 0.94(0.91-0.98) 0.96(0.94-0.99) 0.95(0.92-0.98) 0.94(0.93-0.95) 0.94(0.91-0.97) 0.95(0.93-0.96) 0.98(0.97-0.99) 1.01(nan-nan) 1.03(1.01-1.05) 0.77(0.65-0.91) 0.87(0.82-0.93) 1.38(1.32-1.44) 0.96(0.94-0.97) 0.96(0.95-0.98) 1.06(1.04-1.07) 1.04(1.02-1.06) 1.05(1.03-1.08) 1.06(1.03-1.09) 1.05(1.02-1.09) markers A 0.5 A/Measles A/Other disorders of middle ear and mastoid A/Portal vein thrombosis A/Peptic ulcer, site unspecified A/Femoral hernia A/Hepatic failure, not elsewhere classified A/Obstetric embolism A/Urothelial cancer A/Other endocrine  cancer A/Viral and other specified intestinal infections A/Other gastroenteritis and colitis of infectious and unspecified origin A/Erysipelas A/Other specified infectious agents as the cause of diseases classified A/Acute posthaemorrhagic anaemia A/Other anaemias A/Other coagulation defects A/Other nontoxic goitre A/Thyrotoxicosis [hyperthyroidism] A/Thyroiditis A/Type 1 diabetes mellitus A/Type 2 diabetes mellitus A/Unspecified diabetes mellitus A/Other disorders of pancreatic internal secretion A/Hyperparathyroidism and other disorders of parathyroid gland A/Disorders of lipoprotein metabolism and other lipidaemias A/Disorders of mineral metabolism A/Vascular dementia A/Senile cataract A/Other retinal disorders A/Retinal disorders in diseases classified elsewhere A/Otitis externa A/Nonsuppurative otitis media A/Suppurative and unspecified otitis media A/Perforation of tympanic membrane A/Other disorders of tympanic membrane A/Conductive and sensorineural hearing loss A/Postprocedural disorders of ear and mastoid process, not elsewhere A/Essential (primary) hypertension A/Angina pectoris A/Acute myocardial infarction A/Chronic ischaemic heart disease A/Pulmonary embolism A/Other pulmonary heart diseases A/Nonrheumatic mitral valve disorders A/Nonrheumatic aortic valve disorders A/Cardiac arrest A/Atrial fibrillation and flutter A/Heart failure A/Intracerebral haemorrhage A/Cerebral infarction A/Atherosclerosis A/Other peripheral vascular diseases A/Arterial embolism and thrombosis A/Phlebitis and thrombophlebitis A/Other venous embolism and thrombosis A/Varicose veins of lower extremities A/Other disorders of veins A/Hypotension A/Acute tonsillitis A/Influenza due to identified zoonotic or pandemic influenza virus A/Pneumonia, organism unspecified A/Chronic diseases of tonsils and adenoids A/Other chronic obstructive pulmonary disease A/Asthma A/Other interstitial pulmonary diseases A/Pleural effusion, not elsewhere classified A/Oesophagitis A/Other diseases of oesophagus A/Gastric ulcer A/Duodenal ulcer A/Gastritis and duodenitis A/Inguinal hernia A/Paralytic ileus and intestinal obstruction without hernia A/Diverticular disease of intestine A/Other diseases of anus and rectum A/Haemorrhoids and perianal venous thrombosis A/Fibrosis and cirrhosis of liver A/Cholelithiasis A/Intestinal malabsorption A/Other diseases of digestive system A/Lichen simplex chronicus and prurigo A/Skin changes due to chronic exposure to nonionizing radiation A/Gout A/Other crystal arthropathies A/Coxarthrosis [arthrosis of hip] A/Ankylosing spondylitis A/Other spondylopathies A/Other intervertebral disc disorders A/Dorsalgia A/Other soft tissue disorders, not elsewhere classified A/Calculus of kidney and ureter A/Calculus of lower urinary tract A/Neuromuscular dysfunction of bladder, not elsewhere classified A/Other disorders of bladder A/Gestational [pregnancy-induced] hypertension A/Premature separation of placenta [abruptio placentae] A/Postpartum haemorrhage A/Single spontaneous delivery A/Single delivery by caesarean section A/Maternal infectious and parasitic diseases classifiable elsewhere but A/Congenital malformations of oesophagus A/Cystic kidney disease A/Pancreatic cancer A/Colon cancer A/Non-melanoma cancer A/Breast cancer A/Cervix cancer A/Corpus cancer A/Ovarian cancer A/CUP 90 537 613 710 720 744 1059 193 203 8 9 39 169 236 238 242 263 264 265 267 268 271 273 275 321 324 333 496 505 506 525 528 529 535 536 543 548 557 562 563 567 568 569 575 576 587 589 591 595 597 604 607 608 612 614 615 618 621 628 632 641 650 659 660 677 680 704 706 708 709 712 719 730 731 736 738 746 750 757 759 781 797 842 843 848 869 872 875 877 893 931 932 941 942 1006 1031 1047 1051 1053 1068 1164 1179 182 185 197 212 213 215 216 223 1.6394439669554841 3.8557004226148313 4.136618567099093 15.740015187263365 1.656471010496278 1.598000785099808 2.3715432414423288 3.338515378434197 2.4765896074892084 11.415552862675671 2.1082971958294503 11.115217595198436 1.9469447468557937 11.162470735651109 7.608667179067246 27.23745113906647 3.0577286362298937 10.352453173338684 1.30342192138976 10.52336669111941 41.00873893195053 18.77053190458466 1.4700189174065723 5.181199693360894 38.72507237099319 2.4937744337473373 1.7767804205502842 1.596189589185376 10.031260678930144 2.1305112951558325 1.830120552597344 2.3925457665718577 8.37365113399276 1.3610848452996476 7.050741129415144 2.260136440615008 2.53558801045408 2.277384255521252 4.533547560926653 12.463182359636694 16.299276274952632 247.94414013709462 2.4937744337473373 2.679137439354029 1.4677489699941555 3.332696478815832 6.391927133086423 29.416249683724054 4.235628801440129 7.9754362538368335 12.622082187415955 10.352453173338684 33.59040716486513 240 102.67028689052894 23.822611338497854 21.864624153268593 5.064523889910164 1.7978442828615018 240 2.1981439073773577 7.097187090476315 2.2425754315982016 3.201646766434877 2.420548802102632 8.144962509087131 4.725659674844427 1.5338450838308546 26.09396800220725 66.3304532405828 1.4057393089111134 15.18144510516409 1.8001588557947827 28.99536275397272 9.619670984824658 26.380552203492357 2.6186619614546798 4.968102240011844 1.9899714516698799 32.297157862595924 1.6574813178621923 15.597695313096068 3.498762121475725 1.7055427658653732 5.292350920662522 4.5219213299092536 2.1413378286843594 1.7942184065353426 1.38385587433386 4.887071883612929 3.4743522810184686 1.9469447468557937 1.6585065550698301 1.4628784211935837 13.57843588526943 3.459337155055376 10.3489841414396 3.8778165550145554 240 2.4436736144843105 1.4556060298284248 3.2351885430307123 48.15799802546925 4.225762472897732 5.01153833253812 9.166910459550603 2.5464566595141584 3.7383865833256205 3.4013263439068244 1.6651279640312775 283.0/2330000.0 196.0/2330000.0 650.0/2330000.0 134.0/2330000.0 5068.0/2300000.0 2794.0/2320000.0 2021.0/2320000.0 2040.0/2310000.0 5755.0/2280000.0 15212.0/2230000.0 7083.0/2310000.0 991.0/2320000.0 11698.0/2240000.0 1029.0/2330000.0 767.0/2330000.0 1469.0/2320000.0 15953.0/2250000.0 21856.0/2230000.0 5013.0/2310000.0 25274.0/2250000.0 12168.0/2270000.0 9619.0/2290000.0 9762.0/2310000.0 1732.0/2320000.0 7064.0/2280000.0 1700.0/2320000.0 5191.0/2280000.0 1241.0/2320000.0 3845.0/2320000.0 3355.0/2320000.0 3625.0/2310000.0 2250.0/2320000.0 6870.0/2270000.0 1281.0/2320000.0 7562.0/2280000.0 4176.0/2300000.0 4885.0/2290000.0 1181.0/2320000.0 9665.0/2240000.0 1554.0/2320000.0 7848.0/2300000.0 2934.0/2310000.0 7722.0/2280000.0 1855.0/2330000.0 23192.0/2170000.0 5708.0/2280000.0 601.0/2330000.0 1067.0/2320000.0 322.0/2330000.0 2428.0/2310000.0 22775.0/2080000.0 3522.0/2300000.0 739.0/2330000.0 3623.0/2300000.0 3589.0/2270000.0 898.0/2320000.0 <b>%{text}</b><br>FDR-P: %{hovertext:,.2g}:<br>IRR (95% CI): %{meta}<br>Events/Person-years: %{customdata}<extra></extra> 0.0020521377112524834 0.018660738926095218 0.000008619381634322138 0.01243961841861932 0.00004906166542925342 0.0012288183580517107 5.0679933373850754e-14 0.010675294635760179 0.00005250168674437825 1.856171098132651e-12 2.500660511659257e-7 0.043621869162074015 0.01278026022864937 0.022561745917871703 0.002858989500812202 0.014914900985038563 0.0004586534045232676 0.005932979599856991 4.56677032800398e-92 0.0024357699843578725 0.005867752497823293 0.006775925674836882 0.001149804395021431 3.0416298146853794e-16 1.7443847605123075e-195 2.3779813138779153e-38 0.00016324164063122619 4.6384569246046237e-10 0.043621869162074015 0.027745626779485524 0.0000015271241470783537 2.905279466573199e-14 0.00946306701223755 0.002621624129443445 9.142094529501984e-9 0.016493518435881257 4.587939335936316e-24 0.03095357281711927 0.006018951711263344 0.021011131096213453 1.6792912342440948e-7 0.023661377567180786 0.000016216108200905655 0.029556618189577805 0.02262451687630024 7.284823857222527e-7 0.0008430767515183032 0.004113991205131898 0.003076202052314497 0.0006426834268697969 0.02817649930268847 0.015886605072118587 1.2846460342289194e-10 0.04140929060926235 0.00041896092807372303 0.0030460491546073364 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 #008000 white 0 11.61 11.61 7.290000000000001 6.66 9.72 8.280000000000001 11.07 8.280000000000001 9.72 9.72 9.72 8.1 9.450000000000001 8.1 10.53 9.9 9.450000000000001 9.36 12.6 9.27 9.36 9.36 9.450000000000001 11.43 13.68 12.959999999999999 9.63 11.16 9.450000000000001 9.540000000000001 8.1 7.47 8.549999999999999 10.169999999999998 8.280000000000001 8.549999999999999 7.6499999999999995 9.9 9.450000000000001 9.81 8.370000000000001 9.63 8.459999999999999 9.81 9.27 9.81 10.169999999999998 8.459999999999999 10.26 8.370000000000001 8.73 9.450000000000001 12.330000000000002 8.549999999999999 9.72 9.9 1.29(1.13-1.46) 1.29(1.11-1.49) 0.81(0.75-0.88) 0.74(0.62-0.88) 1.08(1.05-1.11) 0.92(0.88-0.96) 1.23(1.17-1.3) 0.92(0.88-0.96) 1.08(1.05-1.12) 1.08(1.06-1.1) 1.08(1.05-1.11) 0.9(0.84-0.96) 1.05(1.02-1.07) 0.9(0.84-0.96) 1.17(1.08-1.27) 1.1(1.04-1.17) 1.05(1.03-1.07) 1.04(1.02-1.06) 1.4(1.35-1.44) 1.03(1.02-1.05) 1.04(1.02-1.06) 1.04(1.02-1.07) 1.05(1.02-1.07) 1.27(1.2-1.33) 1.52(1.48-1.57) 1.44(1.37-1.52) 1.07(1.04-1.11) 1.24(1.16-1.31) 1.05(1.02-1.09) 1.06(1.02-1.1) 0.9(0.87-0.94) 0.83(0.79-0.87) 0.95(0.93-0.98) 1.13(1.06-1.2) 0.92(0.89-0.94) 0.95(0.92-0.98) 0.85(0.82-0.87) 1.1(1.04-1.17) 1.05(1.02-1.07) 1.09(1.04-1.15) 0.93(0.9-0.95) 1.07(1.03-1.11) 0.94(0.91-0.96) 1.09(1.03-1.15) 1.03(1.01-1.05) 1.09(1.06-1.12) 1.13(1.07-1.2) 0.94(0.91-0.97) 1.14(1.07-1.22) 0.93(0.9-0.96) 0.97(0.96-0.99) 1.05(1.02-1.08) 1.37(1.26-1.5) 0.95(0.92-0.98) 1.08(1.04-1.12) 1.1(1.05-1.16) markers AB 0.5 AB/Other disorders of middle ear and mastoid AB/Portal vein thrombosis AB/Peptic ulcer, site unspecified AB/Thyroid Well-diff  cancer AB/Erysipelas AB/Acute posthaemorrhagic anaemia AB/Other coagulation defects AB/Thyrotoxicosis [hyperthyroidism] AB/Type 1 diabetes mellitus AB/Type 2 diabetes mellitus AB/Unspecified diabetes mellitus AB/Hyperparathyroidism and other disorders of parathyroid gland AB/Disorders of lipoprotein metabolism and other lipidaemias AB/Disorders of mineral metabolism AB/Other disorders of eye and adnexa AB/Suppurative and unspecified otitis media AB/Acute myocardial infarction AB/Chronic ischaemic heart disease AB/Pulmonary embolism AB/Heart failure AB/Cerebral infarction AB/Sequelae of cerebrovascular disease AB/Atherosclerosis AB/Arterial embolism and thrombosis AB/Phlebitis and thrombophlebitis AB/Other venous embolism and thrombosis AB/Varicose veins of lower extremities AB/Other disorders of veins AB/Hypotension AB/Pleural effusion, not elsewhere classified AB/Gastric ulcer AB/Duodenal ulcer AB/Inguinal hernia AB/Crohns disease [regional enteritis] AB/Diverticular disease of intestine AB/Other diseases of anus and rectum AB/Haemorrhoids and perianal venous thrombosis AB/Other diseases of liver AB/Cholelithiasis AB/Other diseases of biliary tract AB/Other diseases of digestive system AB/Cutaneous abscess, furuncle and carbuncle AB/Skin changes due to chronic exposure to nonionizing radiation AB/Decubitus ulcer and pressure area AB/Other soft tissue disorders, not elsewhere classified AB/Female genital prolapse AB/Other noninflammatory disorders of cervix uteri AB/Gestational [pregnancy-induced] hypertension AB/Obstructed labour due to maternal pelvic abnormality AB/Postpartum haemorrhage AB/Single spontaneous delivery AB/Single delivery by forceps and vacuum extractor AB/Pancreatic cancer AB/Non-melanoma cancer AB/Breast cancer AB/Corpus cancer 537 613 710 200 39 236 242 264 267 268 271 275 321 324 522 529 563 567 568 591 597 603 604 608 612 614 615 618 621 680 708 709 719 726 731 736 738 748 750 753 759 763 797 823 893 975 982 1006 1040 1047 1051 1052 182 197 212 215 2.6877934987111547 1.7290711630990636 5.064523889910164 1.9051929412874575 4.309257713478627 2.9105123090793263 13.295163964731534 1.9716201297063125 4.279826743603408 11.731381993876836 6.601945263855523 1.3602957291887148 1.893460303085612 1.646627295949384 2.543787439517037 1.8263796254258955 3.338515378434197 2.2267271449517367 91.34039082938023 2.6133637255796462 2.2315282130115284 2.169031366429599 2.9393760356362013 15.516893643413312 194.7583577161137 37.6237915623799 3.787169049076984 9.333626472157675 1.3602957291887148 1.5568054599362344 5.816125655674781 13.53681208532083 2.0239680844632497 2.581429574358396 8.038954292406912 1.7826866897590998 23.338382333194986 1.5092892152963218 2.2204791409111286 1.677550567507348 6.774873978991862 1.6259599743146365 4.790053366504275 1.5293452585595184 1.6454206859436251 6.137580944753443 3.0741328865335413 2.385736641072692 2.511985142432584 3.1920028992677523 1.5501129653773276 1.798968900525268 9.891216519459244 1.382902209418457 3.3778264770652053 2.5162630926603566 48.0/4940000.0 360.0/4940000.0 540.0/4940000.0 417.0/4940000.0 1557.0/4930000.0 1503.0/4940000.0 690.0/4940000.0 247.0/4940000.0 306.0/4940000.0 1059.0/4920000.0 10666.0/4880000.0 6381.0/4920000.0 5738.0/4920000.0 3864.0/4920000.0 1153.0/4930000.0 3613.0/4910000.0 4300.0/4910000.0 11994.0/4840000.0 31528.0/4730000.0 14839.0/4890000.0 2141.0/4930000.0 1564.0/4930000.0 10313.0/4860000.0 10353.0/4870000.0 88709.0/4350000.0 9949.0/4900000.0 4112.0/4920000.0 9286.0/4890000.0 42774.0/4710000.0 11478.0/4870000.0 5031.0/4930000.0 25834.0/4810000.0 20324.0/4860000.0 20772.0/4890000.0 5806.0/4920000.0 6291.0/4910000.0 3733.0/4930000.0 13718.0/4850000.0 3456.0/4920000.0 10644.0/4840000.0 2488.0/4930000.0 426.0/4940000.0 7142.0/4920000.0 7897.0/4900000.0 4994.0/4910000.0 14121.0/4810000.0 2627.0/4910000.0 16496.0/4830000.0 8648.0/4880000.0 10263.0/4860000.0 4543.0/4910000.0 16801.0/4870000.0 1036.0/4930000.0 3149.0/4910000.0 7955.0/4870000.0 16504.0/4830000.0 3993.0/4930000.0 5763.0/4920000.0 21258.0/4750000.0 48990.0/4600000.0 9074.0/4860000.0 11908.0/4820000.0 1222.0/4930000.0 7601.0/4870000.0 5261.0/4890000.0 1364.0/4930000.0 7499.0/4870000.0 1442.0/4930000.0 1472.0/4940000.0 7662.0/4880000.0 4561.0/4780000.0 <b>%{text}</b><br>FDR-P: %{hovertext:,.2g}:<br>IRR (95% CI): %{meta}<br>Events/Person-years: %{customdata}<extra></extra> 0.005841620160873623 0.009521558131860465 0.043621869162074015 0.000269569838759273 0.034444634348768814 0.00031805498017160384 0.02199031868218486 0.003207935046810969 0.004585046001436099 0.036426298619802684 3.8811515146896953e-7 0.021396673063626755 3.5403394975956703e-13 0.000011740993066566831 0.001149804395021431 0.00007584241762500356 0.000018807900785553426 0.000006412377538964349 2.7665043346354644e-10 2.746436944078697e-9 0.01495074830859509 0.00032306519788340247 0.021214890302167614 0.024703802908695328 0.000009278510196852166 3.7164389317130344e-100 0.005932979599856991 4.942894241399128e-9 0.0044093007011760145 0.03933214851512841 0.0332923512142974 0.00005250168674437825 0.001128395613232956 8.716902956323803e-8 0.0000023741265982994566 1.1053562295239563e-8 1.0702433779926795e-34 2.4718417577876734e-202 1.3168939252815545e-52 0.015886605072118587 3.050825746967659e-9 9.999999999999996e-241 0.00047591196393217624 6.400123890420273e-7 1.8196372248450512e-16 3.843906381874529e-15 0.0033048757747934443 1.0947982905818722e-7 2.746436944078697e-9 1.624093233440522e-51 1.1413501671313972e-7 1.0142413797616617e-11 0.032637520283311565 0.034444634348768814 0.0018349487546347031 1.0390254615111552e-8 0.00004118592746399048 0.0006881475402255501 0.0005967978556983151 0.0071021128911487345 2.398788558131353e-7 9.796914559431159e-10 0.002297367774908658 0.023832101392905796 0.00010164950925085029 0.0052797790022068615 0.0007847240936749334 0.00022815776597178363 7.689555208650067e-12 0.00014951587572311096 0.04056531108480611 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 #8b4513 white 0 5.13 11.07 10.44 11.61 8.280000000000001 7.92 7.83 11.88 7.11 8.1 9.63 9.450000000000001 8.01 9.99 10.35 8.280000000000001 8.280000000000001 9.540000000000001 9.450000000000001 9.63 8.280000000000001 7.92 8.64 8.64 8.73 11.700000000000001 8.459999999999999 8.280000000000001 8.82 8.73 8.549999999999999 9.36 9.36 9.450000000000001 8.280000000000001 9.9 11.61 12.51 12.419999999999998 9.36 10.44 8.1 9.540000000000001 8.370000000000001 7.83 8.280000000000001 9.81 8.459999999999999 8.280000000000001 7.56 9.99 8.370000000000001 9.99 9.72 9.540000000000001 8.459999999999999 9.9 9.63 8.64 9.18 8.370000000000001 9.72 9.81 9.27 8.459999999999999 8.459999999999999 9.450000000000001 8.280000000000001 11.61 8.459999999999999 9.450000000000001 0.57(0.42-0.77) 1.23(1.1-1.39) 1.16(1.05-1.27) 1.29(1.15-1.44) 0.92(0.87-0.97) 0.88(0.83-0.93) 0.87(0.8-0.95) 1.32(1.15-1.53) 0.79(0.7-0.9) 0.9(0.84-0.96) 1.07(1.05-1.09) 1.05(1.02-1.08) 0.89(0.86-0.91) 1.11(1.06-1.15) 1.15(1.08-1.23) 0.92(0.88-0.95) 0.92(0.89-0.95) 1.06(1.04-1.09) 1.05(1.04-1.07) 1.07(1.05-1.09) 0.92(0.87-0.96) 0.88(0.83-0.93) 0.96(0.94-0.98) 0.96(0.94-0.99) 0.97(0.96-0.98) 1.3(1.27-1.33) 0.94(0.91-0.97) 0.92(0.9-0.94) 0.98(0.96-0.99) 0.97(0.95-0.99) 0.95(0.92-0.98) 1.04(1.02-1.06) 1.04(1.02-1.05) 1.05(1.03-1.07) 0.92(0.9-0.95) 1.1(1.07-1.14) 1.29(1.24-1.34) 1.39(1.36-1.42) 1.38(1.33-1.44) 1.04(1.02-1.06) 1.16(1.11-1.22) 0.9(nan-nan) 1.06(1.03-1.09) 0.93(0.91-0.95) 0.87(0.84-0.9) 0.92(0.9-0.94) 1.09(1.04-1.14) 0.94(0.93-0.96) 0.92(0.9-0.95) 0.84(0.82-0.86) 1.11(1.07-1.14) 0.93(0.92-0.95) 1.11(1.04-1.18) 1.08(1.03-1.13) 1.06(1.03-1.09) 0.94(0.92-0.96) 1.1(1.06-1.15) 1.07(1.04-1.1) 0.96(0.94-0.98) 1.02(1.01-1.04) 0.93(0.91-0.95) 1.08(1.05-1.1) 1.09(1.04-1.14) 1.03(1.01-1.04) 0.94(0.92-0.97) 0.94(0.91-0.97) 1.05(1.02-1.07) 0.92(0.88-0.95) 1.29(1.2-1.38) 0.94(0.92-0.97) 1.05(1.02-1.08) markers B 0.5 B/Hereditary factor VIII deficiency B/Disorders of porphyrin and bilirubin metabolism B/Other disorders of middle ear and mastoid B/Portal vein thrombosis B/Pneumonia due to Streptococcus pneumoniae B/Peptic ulcer, site unspecified B/Femoral hernia B/Erythema nodosum B/Thyroid Well-diff  cancer B/Other endocrine  cancer B/Erysipelas B/Streptococcus and Staphylococcus as the cause of diseases classified B/Acute posthaemorrhagic anaemia B/Other coagulation defects B/Sarcoidosis B/Other nontoxic goitre B/Thyrotoxicosis [hyperthyroidism] B/Type 1 diabetes mellitus B/Type 2 diabetes mellitus B/Unspecified diabetes mellitus B/Hyperparathyroidism and other disorders of parathyroid gland B/Postprocedural endocrine and metabolic disorders, not elsewhere classified B/Sleep disorders B/Other disorders of external ear B/Essential (primary) hypertension B/Pulmonary embolism B/Nonrheumatic mitral valve disorders B/Nonrheumatic aortic valve disorders B/Atrial fibrillation and flutter B/Other cardiac arrhythmias B/Intracerebral haemorrhage B/Cerebral infarction B/Sequelae of cerebrovascular disease B/Atherosclerosis B/Aortic aneurysm and dissection B/Other peripheral vascular diseases B/Arterial embolism and thrombosis B/Phlebitis and thrombophlebitis B/Other venous embolism and thrombosis B/Varicose veins of lower extremities B/Other disorders of veins B/Influenza due to identified zoonotic or pandemic influenza virus B/Pleural effusion, not elsewhere classified B/Gastric ulcer B/Duodenal ulcer B/Inguinal hernia B/Crohns disease [regional enteritis] B/Diverticular disease of intestine B/Other diseases of anus and rectum B/Haemorrhoids and perianal venous thrombosis B/Acute pancreatitis B/Other diseases of digestive system B/Pilonidal cyst B/Atopic dermatitis B/Psoriasis B/Skin changes due to chronic exposure to nonionizing radiation B/Decubitus ulcer and pressure area B/Ulcer of lower limb, not elsewhere classified B/Gonarthrosis [arthrosis of knee] B/Other soft tissue disorders, not elsewhere classified B/Calculus of kidney and ureter B/Female genital prolapse B/Other noninflammatory disorders of cervix uteri B/Labour and delivery complicated by fetal stress [distress] B/Postpartum haemorrhage B/Retained placenta and membranes, without haemorrhage B/Single delivery by forceps and vacuum extractor B/Puerperal sepsis B/Pancreatic cancer B/Non-melanoma cancer B/Cervix cancer 240 323 537 613 636 710 720 792 200 203 39 166 236 242 257 263 264 267 268 271 275 330 444 526 557 568 575 576 589 590 595 597 603 604 605 607 608 612 614 615 618 632 680 708 709 719 726 731 736 738 754 759 766 773 784 797 823 830 849 893 931 975 982 1043 1047 1048 1052 1056 182 197 213 2.2334666855342657 2.021291976752229 1.3602957291887148 3.5693287011321964 1.4628784211935837 3.4974977997601004 1.657768476827863 2.4937744337473373 2.3386563027268634 1.4385849564183402 6.411039402684041 1.66965374919441 12.450955089707888 4.9302951684129015 2.9393760356362013 4.1200878314655665 4.725659674844427 5.192980915784201 9.558068644984695 8.561230367570362 1.8253370696699571 3.4907098237256657 1.6733592095389611 1.6072361862086508 5.032521750637524 99.42987299910156 2.2267271449517367 8.306018681642831 2.3556302825734683 1.4052523296446862 1.4776555324691394 4.279826743603408 2.9475386108828747 7.0596377889079545 5.624496126376818 7.956497736834558 33.9705174506323 201.60697933533046 51.880449205691356 1.798968900525268 8.515582597107372 240 3.3224733773520807 6.193811619077812 15.740015187263365 14.415227198092568 2.480844860334366 6.960665889368818 8.561230367570362 50.78938904307114 6.942581093248693 10.993858674762757 1.4862828452669676 1.4628784211935837 2.7363760599623763 7.9833738098458 4.385251149712882 3.162318438165183 3.2241727459577434 2.148612428681364 6.620008031350127 9.008910679491114 2.6387694750583015 1.6228376620972331 3.992894713731916 2.277384255521252 3.105283012881487 3.6417647442426606 11.114098780616722 3.8253126911329582 1.391845189182081 7138.0/41890000.0 38978.0/41730000.0 103140.0/40990000.0 134002.0/40770000.0 51770.0/41460000.0 767088.0/36750000.0 85181.0/41420000.0 3959.0/41890000.0 169903.0/40220000.0 63991.0/41470000.0 18635.0/41690000.0 19846.0/41730000.0 44800.0/41470000.0 <b>%{text}</b><br>FDR-P: %{hovertext:,.2g}:<br>IRR (95% CI): %{meta}<br>Events/Person-years: %{customdata}<extra></extra> 0.02539737411576572 0.03143699766957893 0.0007606242022195508 0.003889790666440278 0.02212921831160521 0.006453314372260607 0.04049927688611511 9.999999999999996e-241 0.0023799138526947572 0.00003858355628976596 0.02306833453717046 3.321938819006852e-7 0.03143699766957893 orange orange orange orange orange orange orange orange orange orange orange orange orange white 0 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.9(0.85-0.95) 1.05(1.02-1.08) 1.04(1.02-1.06) 1.04(1.02-1.05) 1.05(1.02-1.07) 1.02(1.01-1.03) 0.97(0.95-0.99) 1.08(nan-nan) 1.03(1.02-1.05) 1.06(1.04-1.08) 1.08(1.04-1.13) 1.06(1.04-1.08) 0.97(0.95-0.98) markers RhD positive 0.5 RhD/Endocarditis, valve unspecified RhD/Mental and behavioural disorders due to use of tobacco RhD/Mononeuropathies of upper limb RhD/Conductive and sensorineural hearing loss RhD/Other disorders of ear, not elsewhere classified RhD/Essential (primary) hypertension RhD/Nonrheumatic aortic valve disorders RhD/Influenza due to identified zoonotic or pandemic influenza virus RhD/Cholelithiasis RhD/Other systemic involvement of connective tissue RhD/Hypertrophy of breast RhD/Gestational [pregnancy-induced] hypertension RhD/Postpartum haemorrhage 579 348 451 543 546 557 576 632 750 863 963 1006 1047 1.5952111836157112 1.502558937117228 3.1188298599352478 2.410073770102595 1.6550339267393608 2.1902171777857204 1.3925527310365318 240 2.6234387631016505 4.413597745436532 1.6369837590734502 6.478608370323036 1.502558937117228 lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey 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lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey lightgrey white 0 0.7 2 markers Non-significant ABO and RhD 0.7 true 0 1 2 3 5 7 10 11 12 13 14 16 21 23 25 26 31 32 33 37 40 42 43 44 45 56 59 60 66 67 68 71 72 75 76 84 88 90 94 99 100 101 102 104 105 106 108 109 112 114 115 116 117 119 120 121 122 123 124 125 126 127 128 129 130 131 134 135 136 137 138 149 150 153 154 155 156 157 159 160 165 228 229 230 231 232 233 234 235 239 240 241 245 246 247 250 251 253 254 255 256 259 260 261 269 270 272 274 278 279 280 283 285 288 289 291 292 294 296 297 301 303 305 307 308 311 312 313 314 315 316 317 318 319 320 323 329 331 334 336 337 340 345 347 352 355 356 357 364 370 376 377 378 379 381 382 385 386 387 388 390 391 392 393 396 397 398 400 401 403 404 405 406 408 410 413 414 415 417 418 419 421 422 423 424 426 427 428 431 434 436 437 439 447 448 453 455 458 459 460 462 463 467 470 471 472 473 474 475 477 481 487 494 495 499 500 501 502 508 511 512 515 521 523 527 531 533 537 541 549 550 551 554 555 556 565 570 573 578 580 584 593 599 602 609 611 613 620 630 636 637 640 647 652 655 663 664 665 666 667 669 670 671 672 674 676 678 679 681 684 688 692 694 695 698 699 701 702 703 707 710 711 714 718 720 740 743 744 747 749 756 760 761 769 771 772 775 777 778 779 785 786 788 789 791 792 793 795 798 799 805 806 812 813 817 818 821 822 826 827 828 829 832 834 835 844 846 861 862 864 873 879 881 885 889 897 902 906 909 912 914 918 919 925 926 927 934 936 937 938 939 943 946 947 951 953 958 959 960 962 970 976 980 990 995 1001 1002 1003 1004 1005 1008 1015 1018 1020 1022 1026 1029 1030 1044 1049 1058 1059 1060 1065 1075 1076 1077 1078 1079 1080 1082 1083 1084 1085 1086 1087 1088 1092 1093 1094 1095 1096 1098 1101 1104 1106 1111 1122 1123 1124 1128 1130 1131 1132 1133 1135 1136 1137 1138 1139 1140 1141 1142 1143 1144 1145 1146 1150 1153 1154 1155 1156 1157 1158 1159 1160 1161 1162 1163 1165 1166 1167 1168 1169 1170 1172 1173 1174 1175 1176 1178 1181 1182 1183 1184 1185 1187 1188 1189 1190 1192 1193 1194 1195 1196 1198 1199 1200 1202 1206 1209 1210 1211 1212 1214 1215 171 172 173 174 175 176 177 178 179 180 181 183 184 186 187 188 189 192 193 195 199 200 201 202 203 204 205 206 207 208 209 210 211 214 218 220 221 222 4 6 8 9 34 35 36 38 39 41 46 48 51 52 53 54 62 73 74 83 85 86 87 92 93 95 96 97 98 103 107 110 111 113 158 162 163 166 167 168 169 170 225 226 227 236 237 238 242 243 244 249 252 257 258 262 263 264 265 266 267 268 271 273 275 276 277 281 282 284 286 287 290 293 295 299 302 306 309 310 321 322 324 325 326 327 328 330 332 333 335 338 339 341 342 343 344 346 349 350 351 353 354 358 359 360 361 362 363 365 366 367 368 369 371 372 373 374 375 380 383 384 389 394 395 399 402 407 409 411 412 416 420 425 429 430 432 433 435 438 440 441 442 443 444 445 446 449 450 452 454 456 457 461 464 465 466 468 469 476 478 479 480 482 483 484 485 486 488 489 490 491 492 493 496 497 498 503 504 505 506 507 509 510 513 514 516 517 518 519 520 522 524 525 526 528 529 532 534 535 536 539 540 542 544 545 548 552 553 558 559 560 561 562 563 564 566 567 568 569 571 572 574 575 577 581 582 583 585 586 587 588 589 590 591 592 594 595 596 597 598 600 601 603 604 605 606 607 608 610 612 614 615 616 617 618 619 621 622 623 624 625 626 627 628 629 631 633 634 635 638 639 641 642 643 644 645 646 648 649 650 651 653 654 656 657 658 659 660 661 662 673 675 677 680 682 683 685 686 687 689 690 691 693 696 697 700 704 705 706 708 709 712 713 715 716 717 719 721 722 723 724 725 726 727 728 729 730 731 732 733 734 735 736 737 738 739 742 745 746 748 751 752 753 754 755 757 758 759 762 763 764 765 766 767 768 770 773 774 776 780 781 782 783 784 787 790 796 797 800 802 803 804 807 808 809 810 811 814 815 816 819 823 824 825 830 831 833 836 837 838 839 840 841 842 843 845 847 848 849 850 851 852 853 854 855 856 857 858 859 860 865 866 867 868 869 870 871 872 874 875 876 877 878 880 882 883 884 886 887 888 890 891 892 893 894 895 896 898 899 900 901 903 904 905 907 908 910 911 913 915 916 917 920 921 922 923 924 928 929 930 931 932 935 940 941 942 944 945 948 949 950 952 954 955 956 957 961 964 965 966 967 968 969 971 972 973 974 975 977 978 979 981 982 983 984 985 986 987 988 989 991 992 993 994 996 997 998 1007 1009 1010 1011 1012 1013 1014 1016 1017 1019 1021 1023 1024 1025 1027 1028 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1045 1046 1048 1050 1051 1052 1053 1054 1055 1056 1057 1061 1062 1063 1064 1068 1069 1073 1081 1108 1134 1147 1148 1149 1151 1152 1164 1171 1179 1180 1186 1197 1201 1203 1205 1207 182 185 191 194 196 197 198 212 213 215 216 217 219 223 224 0 0 0 1 2 2 2 3 3 3 5 5 5 7 7 7 10 10 10 11 11 11 13 13 13 14 16 16 16 21 21 21 23 23 23 25 25 25 26 26 26 31 32 33 33 33 37 40 40 40 43 43 44 44 45 45 56 59 59 59 60 66 66 67 67 68 68 68 71 71 71 75 76 84 88 90 94 94 94 99 99 99 100 100 100 101 102 104 104 104 105 105 105 106 106 108 108 108 109 109 112 112 112 114 115 116 119 120 120 120 122 124 124 125 125 125 126 126 127 130 134 134 135 135 135 137 137 138 149 149 150 153 153 153 154 155 156 157 157 159 160 160 160 165 165 165 228 228 228 229 229 230 230 231 231 232 232 232 233 233 233 234 234 234 235 235 235 239 239 239 240 240 241 241 245 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1075 1076 1076 1077 1080 1082 1083 1084 1085 1086 1087 1087 1088 1093 1093 1093 1095 1095 1096 1101 1106 1106 1111 1122 1124 1124 1128 1130 1132 1132 1132 1133 1133 1135 1135 1136 1136 1136 1137 1137 1137 1138 1139 1139 1139 1140 1140 1141 1141 1141 1142 1143 1143 1144 1144 1144 1145 1145 1145 1146 1146 1150 1150 1150 1153 1153 1153 1154 1154 1154 1155 1155 1156 1157 1158 1159 1160 1160 1161 1162 1162 1163 1163 1163 1165 1165 1165 1166 1167 1168 1168 1168 1169 1169 1169 1170 1172 1172 1172 1173 1173 1173 1174 1174 1174 1175 1175 1175 1176 1176 1176 1178 1178 1178 1181 1181 1181 1182 1182 1182 1183 1183 1183 1184 1184 1184 1185 1185 1185 1188 1189 1190 1190 1192 1192 1192 1193 1193 1194 1194 1194 1195 1196 1196 1196 1198 1198 1198 1199 1200 1200 1200 1202 1206 1206 1206 1210 1211 1211 1212 1212 1214 1214 1214 1215 1215 1215 171 171 171 172 172 172 173 173 173 174 174 174 175 175 175 176 176 176 177 177 177 178 178 178 179 179 179 180 180 180 181 181 181 183 183 183 184 184 184 186 186 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6245.0/18270000.0 <b>%{text}</b><br>BON-P: %{hovertext:,.2g}:<br>IRR (95% CI): %{meta}<br>Events/Person-years: %{customdata}<extra></extra> 2.8987683972715198e-24 0.00011120528060683008 0.019396959140351302 0.000021650308557928294 0.0397622537845584 1.143256642751907e-12 0.025763374654310132 0.01734371284279573 0.017061425771307304 3.4570375678848003e-26 3.615537266537271e-7 6.850808124055063e-98 1.399081521150541e-60 4.851803195198108e-56 0.007592876602674478 0.04035898488588418 0.0038682920243373366 6.023940207948588e-10 0.0021388919726628712 0.0005941284303103777 1.7401190345056237e-169 1.20680642935552e-87 3.3687282876412462e-93 0.010608452369689408 2.047581819432712e-29 1.3582681361853061e-13 5.739037883189927e-20 1.9105736140225544e-12 0.0018408858994890716 7.887141772639357e-8 0.003292005644330079 0.012127383712754885 4.890340620050825e-7 0.0006241342088678192 1.7306551239751842e-8 0.000010481806549995987 6.518479317261523e-14 8.322597807253671e-7 1.5320099859687397e-8 4.7402926888858096e-14 2.361634995436842e-9 0.011247483106103844 0.00006748421180828534 0.004513547338438226 0.0014364706857426025 0.00026151834263297584 4.759014432907689e-9 0.00029674880097191607 0.008395053173031845 1.2832018559367119e-12 black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black black white 0 0.8 6.5 6.45 5.85 4.5 4.2 5.4 5.45 5.3500000000000005 5.5 5.5 5.3500000000000005 7.8500000000000005 9.45 8.2 5.25 5.3500000000000005 5.6000000000000005 6.949999999999999 7.45 6.949999999999999 7.800000000000001 8.95 8.05 7.55 7.45 8.35 8 5.5 5.6000000000000005 6.2 6.75 4.6000000000000005 4.3 4.1499999999999995 4.699999999999999 4.6000000000000005 4.55 4.6000000000000005 4.050000000000001 4.1499999999999995 5.3500000000000005 5.45 5.15 4.65 4.75 4.35 5.2 5.3500000000000005 6.8999999999999995 5.6000000000000005 1.3(1.24-1.37) 1.29(1.17-1.42) 1.17(1.09-1.26) 0.9(0.86-0.93) 0.84(0.77-0.92) 1.08(1.06-1.1) 1.09(1.04-1.13) 1.07(1.03-1.1) 1.1(1.05-1.15) 1.1(1.08-1.12) 1.07(1.05-1.09) 1.57(1.51-1.64) 1.89(1.75-2.03) 1.64(1.54-1.74) 1.05(1.03-1.08) 1.07(1.03-1.1) 1.12(1.07-1.18) 1.39(1.27-1.52) 1.49(1.26-1.77) 1.39(1.22-1.59) 1.56(1.51-1.61) 1.79(1.69-1.89) 1.61(1.54-1.68) 1.51(1.25-1.83) 1.49(1.39-1.59) 1.67(1.48-1.89) 1.6(1.46-1.76) 1.1(1.07-1.12) 1.12(1.07-1.18) 1.24(1.16-1.33) 1.35(1.18-1.54) 0.92(0.88-0.95) 0.86(0.82-0.9) 0.83(0.76-0.89) 0.94(0.92-0.96) 0.92(0.89-0.95) 0.91(0.89-0.93) 0.92(0.9-0.95) 0.81(0.76-0.86) 0.83(0.79-0.87) 1.07(1.05-1.09) 1.09(1.05-1.13) 1.03(1.02-1.05) 0.93(0.89-0.96) 0.95(0.92-0.97) 0.87(0.83-0.92) 1.04(1.03-1.06) 1.07(1.04-1.1) 1.38(1.19-1.59) 1.12(1.09-1.16) markers Concordant in validation cohort, after bonferroni-adjustment 0.8 A/Other coagulation defects AB/Other coagulation defects B/Other coagulation defects A/Thyrotoxicosis [hyperthyroidism] AB/Thyrotoxicosis [hyperthyroidism] A/Type 2 diabetes mellitus AB/Type 2 diabetes mellitus B/Type 2 diabetes mellitus A/Unspecified diabetes mellitus A/Disorders of lipoprotein metabolism and other lipidaemias A/Chronic ischaemic heart disease A/Pulmonary embolism AB/Pulmonary embolism B/Pulmonary embolism A/Heart failure A/Sequelae of cerebrovascular disease A/Atherosclerosis A/Arterial embolism and thrombosis AB/Arterial embolism and thrombosis B/Arterial embolism and thrombosis A/Phlebitis and thrombophlebitis AB/Phlebitis and thrombophlebitis B/Phlebitis and thrombophlebitis A/Portal vein thrombosis A/Other venous embolism and thrombosis AB/Other venous embolism and thrombosis B/Other venous embolism and thrombosis A/Varicose veins of lower extremities AB/Varicose veins of lower extremities A/Other disorders of veins AB/Other disorders of veins A/Gastric ulcer A/Duodenal ulcer B/Duodenal ulcer A/Inguinal hernia B/Inguinal hernia A/Diverticular disease of intestine A/Haemorrhoids and perianal venous thrombosis AB/Haemorrhoids and perianal venous thrombosis B/Haemorrhoids and perianal venous thrombosis A/Cholelithiasis AB/Cholelithiasis A/Other soft tissue disorders, not elsewhere classified B/Calculus of kidney and ureter A/Gestational [pregnancy-induced] hypertension AB/Gestational [pregnancy-induced] hypertension A/Single delivery by forceps and vacuum extractor AB/Single delivery by forceps and vacuum extractor A/Pancreatic cancer pos/Gestational [pregnancy-induced] hypertension 242 242 242 264 264 268 268 268 271 321 567 568 568 568 591 603 604 608 608 608 612 612 612 613 614 614 614 615 615 618 618 708 709 709 719 719 731 738 738 738 750 750 893 931 1006 1006 1052 1052 182 1006 23.53778648205964 3.9538745896967966 1.7122663490428502 4.664535909747074 1.400529007110326 11.941856266525354 1.588997250871444 1.760857925629579 1.7679846789869027 25.46129590092146 6.441827157690308 97.16425819593573 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0.6666666666666666 #ed7953 0.7777777777777778 #fb9f3a 0.8888888888888888 #fdca26 1 #f0f921 #636efa #EF553B #00cc96 #ab63fa #FFA15A #19d3f3 #FF6692 #B6E880 #FF97FF #FECB52 #2a3f5f white white #E5ECF6 true true white left closest light white #E5ECF6 white white  #E5ECF6 white white  #E5ECF6 white 2 white true  white #E5ECF6 white 2 white true  white #E5ECF6 white 2 white true  white #2a3f5f white white  white white  #E5ECF6 white white  0.05 true white white  15 white 2 true white white  15 white 2 #333333 14 <b>Manhattanplot - Disease catagories/False Discovery Rate Adjusted P-Values In Main Cohort Depending On ABO Blood Group. </b> <br> 1500 y white black 1 0 1215 false true -60 0 inside Infectious Disease Malignant Disease Hematological Disease Endocrine Disease Psychiatric Disease Brain Disease Ophthalmic Disease Ear, Nose and Throat Circulatory Disease Respiratory Disease Gastro-intestinal Disease Dermatological Disease Musculoskeletal Disease Genitourinary Disease Pregnancy and Puerperium Perinatal Disease Congenital Disorders 85 197.5 241.5 295 370.5 443.5 501 536.5 586.5 656.5 724.5 796.5 872 952.5 1031.5 1099 1172 <b> true y white black 1 x 0 1215 false true false 0 black 5 outside 0 171 225 259 332 410 478 525 549 625 689 761 833 912 994 1070 1129 <b> true black 1 -0.5 130 false true 5 outside P 0.05 50 100 1.3010299956639813 50 100 1 <b>-log10(FDR-adjusted p-value) trueheader  Main cohort  Validation cohort         Individuals 4,204,234  1,197,522         Person-years, sum 50 M  22 M         Events, median (IQR) 4748 (869–23,166)  7129 (2464–19,973)          A AB B ABO total RhD positive  A AB B ABO total RhD positive Before adjustment 229 129 179 537 106  64 37 42 143 5 Positive effects, N 150 79 107 336 61  47 23 22 92 3 Negative effects, N 79 50 72 201 45  17 14 20 51 2 After adjustment* 108 56 70 234 13  26 13 10 49 1 Positive effects, N 66 38 36 140 10  19 10 6 35 1 Negative effects, N 42 18 34 94 3  7 3 4 14 0 Positive IRR, median (range) 1.05 (1.01–1.72) 1.09 (1.03–1.52) 1.09 (1.02–1.39)  1.05 (1.02–1.08)  1.1 (1.03–1.57) 1.32 (1.07–1.89) 1.5 (1.07–1.64)  1.12 (1.12–1.12) Negative IRR, median (range) 0.95 (0.77–0.99) 0.92 (0.74–0.97) 0.92 (0.57–0.98)  0.97 (0.9–0.97)  0.92 (0.86–0.95) 0.84 (0.81–0.87) 0.88 (0.83–0.93)  - table2 Table 2. Meta-summary of results.In our validation cohort, consisting of almost 1.2 million blood donors accruing 22 million person-years of follow-up, we validated the findings from the significant disease categories from the first analysis. Among the 143 and 5 significant disease categories for ABO and RhD, respectively, the median number of events was 7129 (IQR 2464–19,973). Before multiple testing adjustment, we identified 160 associations between a blood group in 143 and 5 disease categories, for the ABO and RhD blood group, respectively. After Bonferroni adjustment, there were 49 and 1 associations remaining between ABO and RhD blood group, respectively (Table 2 and Figure 3).0.media/fig3.jpgA number of previously well-established associations were seen among the Bonferroni-adjusted results. For thrombosis, blood group A had a higher risk as compared to blood group O (e.g., pulmonary embolism, IRR 1.57 [95% CI, 1.51–1.64] and portal vein thrombosis, IRR 1.51 [95% CI, 1.25–1.83]). Bleeding disorders were more frequent in blood group O as compared to blood group A (e.g., gastric ulcer, IRR 0.92 [95% CI, 0.88–0.95] and duodenal ulcer, IRR 0.86 [95% CI, 0.82–0.9]). Thyrotoxicosis was also less common in blood groups A and AB as compared to blood group O (with IRRs of 0.90 [95% CI, 0.86–0.93] and 0.84 [95% CI, 0.77–0.92], for A and AB, respectively). Pregnancy-induced hypertension was less common in blood groups A and AB, as compared to blood group O (with IRRs of 0.95 [95% CI, 0.92–0.97] and 0.87 [95% CI, 0.83–0.92] for A and AB, respectively). Pancreatic cancer was the only malignancy that remained associated with a blood group, specifically blood group A as compared to blood group O (IRR, 1.29; 95% CI, 1.19–1.40). A new finding was that of calculus of the kidney and ureter, which were found to be less common in blood group B as compared to blood group O (IRR 0.93 [95% CI, 0.89–0.96]). Cholelithiasis, which has been disputed, was more common in blood groups A and AB as compared to blood group O (with IRRs of 1.07 [95% CI, 1.05–1.09] and 1.09 [95% CI, 1.05–1.13] for A and AB, respectively).In disease categories not significant after Bonferroni adjustment, some findings exhibited particularly strong effects, such as for viral and other specified intestinal infections, where blood group AB had a significantly lower risk, as compared to blood group O (IRR 0.74; 95% CI, 0.62–0.87). There was a lower risk for ankylosing spondylitis in blood group AB as compared to blood group O (IRR 0.79; 95% CI, 0.67–0.94), and for acute pancreatitis, again with a lower risk in blood group AB as compared to blood group O (IRR 1.14; 95% CI, 1.04–1.24). For the RhD positive as compared to RhD negative, only one disease category remained statistically significant after Bonferroni adjustment, namely pregnancy-induced hypertension (IRR 1.12; 95% CI, 1.09–1.16). Strong effects identified in the main cohort, but not in the validation cohort were hereditary factor VIII deficiency in blood group B (IRR 0.57; 95% CI, 0.42–0.77), well-differentiated thyroid cancer in blood groups AB (IRR 0.74; 95% CI, 0.62–0.88) and B (IRR 0.79; 95% CI, 0.70–0.90), measles in blood group A (IRR 1.72; 95% CI, 1.23–2.39), as well as both erythema nodosum (IRR 1.32; 95% CI, 1.15–1.53) and sarcoidosis in blood group B (IRR 1.15; 95% CI, 1.08–1.23), as compared to blood group O.DiscussionIn this large cohort study of 5.1 million unique persons followed over 70 million person-years, we performed an agnostic analysis of associations between the ABO and RhD blood groups and the risk of 1217 distinct disease categories. After multiple testing adjustment and comparison with a validation cohort, 49 and 1 associations between disease categories and blood group for ABO and RhD remained significant, respectively. Overall, we were able to confirm a number of previously known associations such as risk of thrombosis and hemorrhagic events. In addition, we also identified novel associations, some with firm evidence and valid even after conservative Bonferroni adjustment, in the validation cohort, including calculus of the kidney and ureter. Furthermore, being the largest study so far, we also found that blood groups A and AB had a lower risk of gestational hypertension, compared to blood group O, which has previously been disputed bib5 bib10 bib15. Of the identified associations, we speculate that some associations may be driven by increased screening due to other concomitant diseases that are associated with blood groups, which might be the case for hyperlipidemias that are screened for in heart disease. Most of the investigated disease or disease groups, however, do not seem to be strongly influenced by the ABO blood group of the individual. As to possible mechanisms explaining the associations identified, we may only generate hypothesis to be further tested. It is however peculiar to identify a condition, such as renal caliculi, with highly variable distribution, in regard to geographic region, to have an association to blood group. A possible mechanism could be, when considering the full spectrum of disease categories investigated, that lower urine pH in diabetic patients, a disease category associated with an increased incidence in blood group B, may result in altered stone formation bib21.In previous studies, intending to dissect the association between blood groups and disease, there is diversity in findings and non-findings, something that may be a consequence of ethnic or geographic group, sample size, complexity of statistical modeling, or disease classifications used. This, however, imposes difficulties when comparing our results to the vast number of studies available concentrating the mentioned discoveries to a select few disease categories.This is hitherto the largest study investigating blood group antigens and disease occurrence in an effort to find novel and confirm previously known associations. There are some particular strengths to our approach and data. Most notably, the study was based on a very large study population, representing one third of the Swedish population, with long-term and unbiased follow-up. This ensures both the reliability and the generalizability of the results. The agnostic approach also has the advantage of not being based on specific pre-set conceptions of specific disease categories and possible associations of blood group. All disease categories are treated equally and investigated using the same principles effectively removing researcher bias. Moreover, the data has been collected prospectively in various high-quality healthcare registries during a long time period with almost complete coverage. In addition, the fact that all blood group data in the SCANDAT3-S database were collected from clinical transfusion registers – the quality of which is essential for the safe administration of blood transfusions – ensures that there should be little or no errors in the blood group coding. Similarly, while the validity of the outcomes registration certainly varies between the different disease categories, the degree of such misclassification is unlikely to vary between blood groups, and so it should not affect the magnitude of point estimates.The current study is limited by several factors. One such factor is the disease classification scheme used, based primarily on ICD revision 10 categories that in some instances may lack precision. Smaller disease entities were not accounted for and thus there may be true associations that were missed. It is thus possible that some of the associations that we reported were driven by multiple unknown associations within a specific disease category that may have unequal, or even detrimental, effects on the outcome. However, we believe that this limitation is an opportunity for further sub-categorized investigations in the future when even more events and follow-up time are available.Another limitation that prevents strong casual inference is the possibility some of the observed associations between ABO blood group and disease categories were driven by other disease associations with ABO blood group. This might, for example, be the case for the associations between blood group A and diabetes as well as hyperlipidemia, which are potentially driven not by a causal association but possibly instead by an association between blood group A and ischemic heart disease, at the occurrence of which diabetes and lipid disorders are screened for and thus frequently diagnosed. We cannot exclude the possibility that some of the other associations were driven by similar non-causal mechanisms.To limit the possibility of false-positive findings, we handled over-dispersed Poisson models using Quasi-Poisson and also in the main cohort applied the FDR approach, described by Benjamini and Hochberg, and then utilized a Bonferroni adjustment on the sub-grouped outcomes in the validation cohort. The aim of this approach was to reduce type one errors without being overly conservative by first conducting an explorative analysis in the main cohort. We also employed a confirmatory analysis with a validation cohort to further limit the possibility of false-positive findings. However, because the validation cohort was both smaller and consisted only of blood donors, who were selected for their good health, the ensuing smaller number of events may result in failure to detect potentially interesting associations. Furthermore, selecting explicitly healthy donors with no known serious health issue at time of start of donation may result in failure to detect less common or specifically non-acquired or early acquired disease. However, in the validation cohort, only approximately 1% of the categories had fewer events than 50 and all findings from the main cohort can be seen in the live Supplementary files 1 and !number(2) and Supplementary files 5–!number(8). It may still be informative to consider also some of the associations from the main cohort that were not corroborated in the validation cohort. This is exemplified by pancreatic cancer where we saw an increased risk in blood groups AB and B in the main cohort (IRR 1.37 and 1.129, p<0.00001 and p<0.00001 for AB and B, respectively) and a similar, yet non-significant effect in the validation cohort (IRR 1.14 and 1.26, p-value 0.8 and 0.6 for B and AB, respectively). This also expands to the non-findings in terms of cancerous disease were multiple relationships that have previously been demonstrated, but not in the validation cohort after Bonferroni adjustment bib28. This strengthens our decision to not limit the presentation of findings to only disease categories identified in the conservative Bonferroni-adjusted analysis.Still, after these limitations we believe that our findings support and generate strong further evidence for previously known associations and indicate new and interesting relationships for disease such as calculus of the kidney and ureter, pregnancy-induced hypertension, well-differentiated thyroid cancer, and sarcoidosis. The new set of associations should be validated in other cohorts but also investigated using a mechanistic approach for a possible causal and biological interaction.