Trans-ancestry analysis reveals genetic and nongenetic associations with COVID-19 susceptibility and severity

Nat Genet. 2021 Jun;53(6):801-808. doi: 10.1038/s41588-021-00854-7. Epub 2021 Apr 22.

Abstract

COVID-19 presents with a wide range of severity, from asymptomatic in some individuals to fatal in others. Based on a study of 1,051,032 23andMe research participants, we report genetic and nongenetic associations with testing positive for SARS-CoV-2, respiratory symptoms and hospitalization. Using trans-ancestry genome-wide association studies, we identified a strong association between blood type and COVID-19 diagnosis, as well as a gene-rich locus on chromosome 3p21.31 that is more strongly associated with outcome severity. Hospitalization risk factors include advancing age, male sex, obesity, lower socioeconomic status, non-European ancestry and preexisting cardiometabolic conditions. While non-European ancestry was a significant risk factor for hospitalization after adjusting for sociodemographics and preexisting health conditions, we did not find evidence that these two primary genetic associations explain risk differences between populations for severe COVID-19 outcomes.

MeSH terms

  • ABO Blood-Group System / genetics
  • Blood Grouping and Crossmatching
  • COVID-19 / genetics*
  • Chromosomes, Human, Pair 3
  • Databases, Genetic
  • Disease Susceptibility
  • Female
  • Galactosyltransferases / genetics
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Patient Acuity
  • Racial Groups
  • Risk Factors

Substances

  • ABO Blood-Group System
  • ABO protein, human
  • Galactosyltransferases