Associations of ABO and Rhesus D Blood Groups with Phenome-Wide Disease Incidence: A 41-year Retrospective Cohort Study of 482,914 Patients

Abstract

AbstractBackgroundThe natural selection responsible for the observed blood group frequency differences between populations remains debatable. The ABO system has been associated with several diseases and recently also with susceptibility to COVID-19 infection. Associative studies of the RhD system and diseases are sparser. A large disease-wide risk analysis may further elucidate the relationship between the ABO/RhD blood groups and disease incidence.MethodsWe performed a systematic log-linear quasi-Poisson regression analysis of the ABO/RhD blood groups across 1,312 phecode diagnoses. Unlike prior studies, we determined the uniqueness of each individual ABO blood group as opposed to using blood group O as the reference. Moreover, we used up to 41-years of nationwide Danish follow-up data, and a disease categorization scheme specifically developed for diagnosis-wide analysis. Further, we determined associations between the ABO/RhD blood groups and the age at the first diagnosis. Estimates were adjusted for multiple testing.ResultsThe retrospective cohort included 482,914 Danish patients (60.4% females). The incidence rate ratios (IRRs) of 101 phecodes were found statistically significant between the ABO blood groups, while the IRRs of 28 phecodes were found statistically significant for the RhD blood group. The associations included cancers and musculoskeletal-, genitourinary-, endocrinal-, infectious-, cardiovascular-, and gastrointestinal diseases.ConclusionsWe found associations of disease-wide susceptibility differences between the blood groups of the ABO and RhD systems, including cancer of the tongue, monocytic leukemia, cervical cancer, osteoarthrosis, asthma, and HIV- and hepatitis B infection. This may indicate that the ABO/RhD blood groups are the results of a selective pressure driven partly by robustness to disease. We found marginal evidence of associations between the blood groups and disease onset.FundingNovo Nordisk Foundation and the Innovation Fund Denmark