Genetic ancestry effects on the response to viral infection are pervasive but cell type specific

Haley E. Randolph, Jessica K. Fiege, Beth K. Thielen, Clayton K. Mickelson, Mari Shiratori, João Barroso-Batista, Ryan A. Langlois, Luis B. Barreiro

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear cells from European- and African-ancestry males. Genetic ancestry effects are common but highly cell type specific. Higher levels of European ancestry are associated with increased type I interferon pathway activity in early infection, which predicts reduced viral titers at later time points. Substantial population-associated variation is explained by cis-expression quantitative trait loci that are differentiated by genetic ancestry. Furthermore, genetic ancestry-associated genes are enriched among genes correlated with COVID-19 disease severity, suggesting that the early immune response contributes to ancestry-associated differences for multiple viral infection outcomes.

Original languageEnglish (US)
Pages (from-to)1127-1133
Number of pages7
Issue number6571
StatePublished - Nov 26 2021

Bibliographical note

Publisher Copyright:
© 2021 American Association for the Advancement of Science. All rights reserved.


  • Adult
  • African Americans/genetics
  • Aged
  • COVID-19/genetics
  • Disease Susceptibility
  • Gene Expression Regulation
  • Genetic Variation
  • Humans
  • Influenza A Virus, H1N1 Subtype/immunology
  • Influenza, Human/genetics
  • Interferon Type I/immunology
  • Leukocytes, Mononuclear/immunology
  • Male
  • Middle Aged
  • Quantitative Trait Loci
  • Severity of Illness Index
  • Single-Cell Analysis
  • Transcription, Genetic
  • Viral Load
  • Whites/genetics
  • Young Adult

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural


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