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Background: The ABO gene contains three major alleles that encodes different antigens; A, B, and O, which determine an individual’s blood group. Previous studies have primarily focused on identifying associations between ABO blood groups and diseases risk. Here, we sought to test for association between ABO genotypes (OO, OA, AA; OB, BB, and AB) and a large set of diseases and disease-related protein biomarkers.

Methods: We conducted association studies in two European cohorts; UK Biobank and NSPHS. We first tested for association by conducting a likelihood ratio test, testing whether ABO contributed significantly to the risk for 24 diseases, and 438 plasma proteins. For phenotypes with FDR< 0· 05, we tested for pair-wise differences between genetically determined ABO genotypes using logistic or linear regression.

Findings: Our study confirmed previous findings of a strong association between ABO and cardiovascular disease, and provide additional evidence of significant differences between heterozygous and homozygous allele carriers for pulmonary embolism, deep vein thrombosis, but also for von Willebrand factor levels. Additionally, we found that ABO contributed significantly to 39 plasma proteins, of which 24 have never been linked to the ABO locus before.

Interpretation: These results show the need of incorporating ABO genotype information in the consultation and management of patients at risk, rather than classifying patients into blood groups. Furthermore, the results indicated an additive effect between genotypes.