Ancestry shapes genetic immune responses
Selection for genes affecting the immune system can vary among populations because of selection for local environments. In humans, ancestry has been associated with different responses to infection. Randolph et al. examined the molecular determinants of these observations using single-cell RNA sequencing of immune cells from individuals of European and African descent who were infected with influenza in vitro. The experiments showed that infection-induced gene signatures diverged in a cell-type-specific manner that was correlated with ancestry, and that these observed ancestry-related differences were caused by changes in gene regulation and processes involved in transcription and translation. —LMZ
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 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.
