Characterization of the human ABO genotypes and their association to common inflammatory and cardiovascular diseases in the UK Biobank

Abstract

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 common inflammatory and cardiovascular diseases in UK Biobank as well as disease‐related protein biomarkers in 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. Our study confirmed previous findings of a strong association between ABO and cardiovascular disease, identified associations for both type 1 and type 2 diabetes, 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. Furthermore, the results indicated an additive effect between genotypes, even between the two most common A subgroups, A1 and A2. Additionally, we found that ABO contributed significantly to 39 plasma proteins, of which 23 have never been linked to the ABO locus before. 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.

The Clinical Utility of ABO and RHD Systems as Potential Indicators of Health Status, a Preliminary Study in Greek Population

“…Moreover, a couple of studies related to the ABO phenotype present links between genetically determined human ABO blood groups with increased risk of various infectious diseases [ 27 ]. The molecular level of ABO blood groups and their association with various diseases should be evaluated, too [ 28 , 29 ].…”

ABO and Rhesus blood groups and multiple health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies

“…In addition, J. Höglund et al found 39 plasma proteins were associated with variation at the ABO locus. For example, proteins with functions related to tumorigenesis (CA9, Gal-9, and KLK6) and pro-inflammatory or anti-inflammatory functions (IFN-gamma-R1, IL-18BP, and MARCO) [ 6 ]. Generally, the overexpression of these proteins leads to an abnormal cell proliferation or cell growth.…”

ABO Blood Groups as a Disease Marker to Predict Atrial Fibrillation Recurrence after Catheter Ablation

“…The United Biobank investigation suggests that the ABO genotypes are strongly associated with common inflammatory and CV diseases. In addition, the ABO blood groups are associated with different levels of VWF and platelet endothelial cell adhesion molecule-1 [ 9 ].…”

“…Despite mounting evidence supporting the critical link between inflammation and AF recurrence, some studies suggest the increased levels of these inflammatory biomarkers simply represent the signs of local inflammation and myocardial injury after catheter ablation and are not as valuable as a predictor of AF recurrence [ 8 ]. Numerous studies demonstrated the association of ABO blood groups with inflammation, thromboembolism, aging diseases, and CV diseases [ 9 ]. Patients with non-O-type blood groups (A, B, or AB type) have a higher risk of thromboembolic events such as coronary artery diseases, cerebrovascular ischemic events, and peripheral vascular disease than those with the O-type blood group [ 10 ].…”