Genetic ancestry shapes context-dependent immune regulation across Indigenous South American populations
- 1Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA
Abstract
Human immune responses remain poorly characterized across Indigenous South American (ISA) populations, limiting our understanding of human immune variation. Here, we generated a single-cell transcriptional atlas of 1.4 million peripheral blood mononuclear cells from 345 individuals representing 13 South American populations, profiled at baseline and following stimulation with lipopolysaccharide, influenza A virus, or Trypanosoma cruzi. Genetic ancestry was associated with the expression of a large fraction of the transcriptome, often only after stimulation, and explained more variation than age or sex. On average, cis-eQTLs accounted for one-quarter of these ancestry-associated differences. Thousands of regulatory variants were common in ISA populations but rare or absent in European reference datasets. Integrating eQTLs with GWAS revealed stimulation-specific disease-associated regulatory variants and an enrichment of ancestry-associated expression differences among genes with colocalizing signals. Our findings highlight the importance of studying diverse populations across immune contexts to understand the genetic architecture of human immune responses.
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BibTeX
@misc{choy2026genetic,
title = {{Genetic ancestry shapes context-dependent immune regulation across Indigenous South American populations}},
author = {C. Choy and L. Vicuna and M. Patino and D. S. Araujo and D. Obispo and M. L. Guevara-Fujita and S. Fonseca and D. Scariot and C. Araujo and J. R. Guerreiro and O. Acosta and C. Johnson and K. Meier and A. Dumaine and K. Williams and T. Lima and T. Rodrigues and A. Khayat and E. Wu and A. Gupta and R. Aguirre-Gamboa and B. Chak and J. Barroso-Batista and F. Capetillo and K. Marcelain and I. Fuentes and J. Gonzalez and P. Beltran and Y. Flores and T. Coronel and J. Latorre and J. Boutaud and C. K. Mickelson and R. Langlois and E. Scott and J. Guerreiro and T. Hünemeier and R. Fujita and L. B. Barreiro},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.21.26365630},
url = {https://www.medrxiv.org/content/10.64898/2026.10.21.26365630v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Genetic ancestry shapes context-dependent immune regulation across Indigenous South American populations
AU - C. Choy
AU - L. Vicuna
AU - M. Patino
AU - D. S. Araujo
AU - D. Obispo
AU - M. L. Guevara-Fujita
AU - S. Fonseca
AU - D. Scariot
AU - C. Araujo
AU - J. R. Guerreiro
AU - O. Acosta
AU - C. Johnson
AU - K. Meier
AU - A. Dumaine
AU - K. Williams
AU - T. Lima
AU - T. Rodrigues
AU - A. Khayat
AU - E. Wu
AU - A. Gupta
AU - R. Aguirre-Gamboa
AU - B. Chak
AU - J. Barroso-Batista
AU - F. Capetillo
AU - K. Marcelain
AU - I. Fuentes
AU - J. Gonzalez
AU - P. Beltran
AU - Y. Flores
AU - T. Coronel
AU - J. Latorre
AU - J. Boutaud
AU - C. K. Mickelson
AU - R. Langlois
AU - E. Scott
AU - J. Guerreiro
AU - T. Hünemeier
AU - R. Fujita
AU - L. B. Barreiro
PY - 2026
DA - 2026/10/21
PB - medRxiv
DO - 10.64898/2026.10.21.26365630
UR - https://www.medrxiv.org/content/10.64898/2026.10.21.26365630v1
AB - Human immune responses remain poorly characterized across Indigenous South American (ISA) populations, limiting our understanding of human immune variation. Here, we generated a single-cell transcriptional atlas of 1.4 million peripheral blood mononuclear cells from 345 individuals representing 13 South American populations, profiled at baseline and following stimulation with lipopolysaccharide, influenza A virus, or Trypanosoma cruzi. Genetic ancestry was associated with the expression of a large fraction of the transcriptome, often only after stimulation, and explained more variation than age or sex. On average, cis-eQTLs accounted for one-quarter of these ancestry-associated differences. Thousands of regulatory variants were common in ISA populations but rare or absent in European reference datasets. Integrating eQTLs with GWAS revealed stimulation-specific disease-associated regulatory variants and an enrichment of ancestry-associated expression differences among genes with colocalizing signals. Our findings highlight the importance of studying diverse populations across immune contexts to understand the genetic architecture of human immune responses.
ER -