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

Elife. 2021 Apr 27:10:e65658. doi: 10.7554/eLife.65658.

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.

Keywords: ABO blood group; RhD blood group; agnostic; all disease; epidemiology; global health; medicine; none.

Plain language summary

The blood types that many people are familiar with, such as O-negative or AB-positive, are determined by two systems of antigens or proteins on the surface of the red blood cells: the ABO system and the RhD system. The ABO system types people’s blood as A, B or AB if they have A and/or B antigens, or as type O if they have neither; while the RhD system provides the positive or negative label depending on whether or not the RhD antigen is present. Previous studies have found that some ABO blood groups are linked to increased risk and severity of a variety of conditions, including blood clots in veins, bleeding disorders and gastric ulcers. Despite the known influence that blood groups can have on disease, the connection has not been fully studied in many conditions, particularly for RhD status. Knowing the differences in risk and disease severity between different populations could help clinicians identify individuals that they need to monitor more closely and include blood group information in prediction models. To fill this gap in information, Dahlén et al. systematically looked for relationships between diseases and blood groups using records from 5.1 million people on a Swedish national blood donation-transfusion database. Examining 1,217 disease categories revealed that the vast majority did not appear to have a connection to either the ABO or RhD systems of classifying blood. However, the analysis identified 49 diseases with links to ABO blood types and one linked to RhD status. One notable finding was that people with blood group B have an decreased risk of kidney stones. The distribution of blood groups varies significantly around the world, so this relationship between disease and blood group may in part explain regional differences in disease occurrence. In the future, identifying relationships with blood groups may help to better understand the underlying biological mechanisms of diseases and lead to new avenues of research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System*
  • Adult
  • Aged
  • Blood Donors
  • Blood Transfusion
  • Databases, Genetic
  • Disease Susceptibility*
  • Female
  • Humans
  • Hypertension, Pregnancy-Induced / blood
  • Hypertension, Pregnancy-Induced / epidemiology
  • Kidney Calculi / blood
  • Kidney Calculi / epidemiology
  • Kidney Calculi / prevention & control
  • Male
  • Middle Aged
  • Pregnancy
  • Protective Factors
  • Rh-Hr Blood-Group System / blood*
  • Risk Assessment
  • Risk Factors
  • Sweden / epidemiology
  • Young Adult

Substances

  • ABO Blood-Group System
  • Rh-Hr Blood-Group System
  • Rho(D) antigen

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.