Genetic ancestry shapes context-dependent immune regulation across Indigenous South American populations
Year: 2026
Type: preprint
Study design: Observational Study
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.
Source: medRxiv
Authors: Cecily Choy, Lucas Vicuña, Maria Patiño, Daniel S. Araujo, Daisy Obispo, Maria Luisa Guevara-Fujita, Susanne Fonseca, Débora Scariot, Cherly Araujo, João Ricardo Guerreiro, Oscar Acosta, Camille Johnson, Kevin Meier, Anne Dumaine, Kelly Williams, Thaynara Lima, Thaissa Rodrigues, André Khayat, Evan Wu, Akansha Gupta, Raúl Aguirre-Gamboa, Bridget Chak, João Barroso-Batista, Fabiola Capetillo, Katherine Marcelain, Ignacia Fuentes, Javiera González, Percibal Beltrán, Yolanda Flores, Teresa Coronel, Josefina Latorre, Joaquín Boutaud, Clayton K. Mickelson, Ryan Langlois, Evan Scott, João Guerreiro, Tábita Hünemeier, Ricardo Fujita, Luis B. Barreiro
Institutions: University of Chicago, Pontificia Universidad Católica de Chile, Universidad de San Martín de Porres, Universidade Federal do Pará, Northwestern University, Chemistry of Life Processes Institute, University of Virginia, Universidade Federal do Rio Grande do Sul, University of Chile, Universidad del Desarrollo, Clínica Alemana, University of Minnesota, Universitat Pompeu Fabra, Institut de Biologia Evolutiva, Chan Zuckerberg Biohub Chicago
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7223140197