An agnostic study of associations between ABO and RhD blood group and phenome-wide disease risk

Abstract

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.

Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus

“…Several association studies have found a relationship between RhD-negativity and enhanced resistance to viral infection (Flegr, 2013; Flegr, Hoffmann and Dammann, 2015; Zietz, Zucker and Tatonetti, 2020; Dahlén et al ., 2021). However, systemic analysis of immune activity by RhD status had never been carried out.…”

“…The distribution of blood groups, including RhD, varies globally-this may explain, at least in part, the regional differences in disease occurrence. RhD-negativity is particularly enriched in East Asian populations (28% RhD-negative) compared with European or African populations (16% and 6%, respectively) (Dahlén et al ., 2021). This may reflect the different historic disease burdens on these populations.…”

“…Although less well studied, RhD status is also known to influence several other health outcomes (Dahlén et al ., 2021). An agnostic analysis of 1217 disease states found an association between RhD status and hypertension during pregnancy (Dahlén et al ., 2021).…”

“…Although less well studied, RhD status is also known to influence several other health outcomes (Dahlén et al ., 2021). An agnostic analysis of 1217 disease states found an association between RhD status and hypertension during pregnancy (Dahlén et al ., 2021). Several studies have demonstrated that RhD-positive and -negative subjects differ in resistance to the pathological effects of aging, fatigue, and smoking (Flegr, Hoffmann and Dammann, 2015).…”

Human exposome assessment platform

“…We have also contributed to a “disease wide association study,” where different causes of hospitalization and death were assessed by blood type. 24 This study is relevant to HEAP, as it demonstrates how methods based on false discovery rates from genetic epidemiology can be applied to other epidemiologic study designs.…”