Genetic Ancestry and Natural Selection Drive Population Differences in Immune Responses to Pathogens
Open accessAbstract
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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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].”
From Functional implications of Neandertal introgression in modern humans (2017) · cites this paper as [9]
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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.
- ORCID
- 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
- bronze
- doi.org
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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