Cited by 516Genetic Associations and EpidemiologyEvolution and Genetic DynamicsRace, Genetics, and Society

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

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Nédélec, Yohann, Sanz, Joaquín, Baharian, Golshid, Szpiech, Zachary A., Pacis, Alain, Dumaine, Anne, Grenier, Jean-Christophe, Freiman, Andrew +10 more·2016·Cell

Abstract

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.

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Crossref · 10.1016/j.cell.2016.09.025

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  • Selected variants can exert their effect by modifying gene expression or by changing the amino acid sequence.

    “Selected variants can exert their effect by modifying gene expression or by changing the amino acid sequence [8–12].”

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Authors
Nédélec, Y., Sanz, J., Baharian, G., Szpiech, Z. A., Pacis, A., Dumaine, A., Grenier, J.-C., Freiman, A., Sams, A. J., Hebert, S., Pagé Sabourin, A., Luca, F., Blekhman, R., Hernandez, R. D., Pique-Regi, R., Tung, J., Yotova, V., & Barreiro, L. B.
Affiliations
  • CHU Sainte-Justine Research Center (CA)
  • University of California, San Francisco (US)
  • Wayne State University (US)
  • Cornell University (US)
  • University of Minnesota (US)
  • Duke University (US)
Corresponding author
Barreiro, Luis B.
Venue
Cell
Publisher
Elsevier BV
Published
2016-10
Volume
167
Issue
3
Pages
657-669.e21
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2538361155
Cited by
512
References
75
Citations by year
2026: 35 · 2025: 36 · 2024: 55 · 2023: 55 · 2022: 59 · 2021: 79 · 2020: 57 · 2019: 52 · 2018: 43 · 2017: 34 · 2016: 4 · 2015: 1 · 2013: 1
FWCI
35.81
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research (232519, 301538)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Race, Genetics, and Society
Keywords
genetic ancestry, African ancestry, European ancestry, macrophages, immune response to bacterial infection, expression quantitative trait loci, cis-eQTL, trans-eQTL, natural selection, inflammation, intracellular bacterial growth

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