Genetic Ancestry Effects on the Response to Viral Infection Are Pervasive but Cell Type Specific

Overview

Journal Science

Specialty Science

Date 2021 Nov 25

PMID 34822289

Citations 50

Authors

Haley E Randolph

Jessica K Fiege

Beth K Thielen

Clayton K Mickelson

Mari Shiratori

Joao Barroso-Batista

Ryan A Langlois

Luis B Barreiro

Affiliations

Soon will be listed here.

Abstract

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 cisexpression 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.

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