Genetic Ancestry and Natural Selection Drive Population Differences in Immune Responses to Pathogens.

Journal Article

Individuals from different populations vary considerably in their susceptibility to immune-related diseases. To understand how genetic variation and natural selection contribute to these differences, we tested for the effects of African versus European ancestry on the transcriptional response of primary macrophages to live bacterial pathogens. A total of 9.3% of macrophage-expressed genes show ancestry-associated differences in the gene regulatory response to infection, and African ancestry specifically predicts a stronger inflammatory response and reduced intracellular bacterial growth. A large proportion of these differences are under genetic control: for 804 genes, more than 75% of ancestry effects on the immune response can be explained by a single cis- or trans-acting expression quantitative trait locus (eQTL). Finally, we show that genetic effects on the immune response are strongly enriched for recent, population-specific signatures of adaptation. Together, our results demonstrate how historical selective events continue to shape human phenotypic diversity today, including for traits that are key to controlling infection.

Full Text

Duke Authors

Cited Authors

  • Nédélec, Y; Sanz, J; Baharian, G; Szpiech, ZA; Pacis, A; Dumaine, A; Grenier, J-C; Freiman, A; Sams, AJ; Hebert, S; Pagé Sabourin, A; Luca, F; Blekhman, R; Hernandez, RD; Pique-Regi, R; Tung, J; Yotova, V; Barreiro, LB

Published Date

  • October 2016

Published In

Volume / Issue

  • 167 / 3

Start / End Page

  • 657 - 669.e21

PubMed ID

  • 27768889

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2016.09.025

Language

  • eng