Key Points: We extracted 210 412 blood group alleles (∼8.5 × 109 bp) from 1000 Genomes and matched them against official blood group reference lists. Of 1241 nonsynonymous variants found, 241 are known blood group polymorphisms while 1000 may represent undiscovered or altered antigens.

Background: There are multiple known associations between the ABO and RhD blood groups and disease. No systematic population-based studies elucidating associations between a large number of disease categories and blood group have been conducted.Methods: Using SCANDAT3-S, a comprehensive nationwide blood donation-transfusion database, we modeled outcomes for 1217 disease categories including 70 million person-years of follow-up, accruing from 5.1 million individuals.Results: We discovered 49 and 1 associations between a disease and ABO and RhD blood groups, respectively, after adjustment for multiple testing. We identified new associations such as a decreased risk of kidney stones and blood group B as compared to blood group O. We also expanded previous knowledge on other associations such as pregnancy-induced hypertension and blood groups A and AB as compared to blood group O and RhD positive as compared to negative.Conclusions: Our findings generate strong further support for previously known associations, but also indicate new interesting relations.Funding: Swedish Research Council.