Summary
A medRxiv preprint analysed gene activity in 1.4 million immune cells from 345 people across 13 Indigenous South American populations. Genetic ancestry was associated with many expression differences, often after immune stimulation.
A medRxiv preprint reports a single-cell atlas of immune activity in Indigenous South American populations, based on 1.4 million peripheral blood mononuclear cells (PBMCs) from 345 people across 13 populations. The researchers found that genetic ancestry was associated with expression across a large fraction of the genes measured, with many differences appearing only after immune stimulation.
How the immune cells were studied
PBMCs are a group of immune cells found in blood. The researchers profiled them at baseline and after stimulation with lipopolysaccharide (LPS), influenza A virus or Trypanosoma cruzi. LPS is a bacterial component used to trigger immune responses; the other two challenges represent a virus and a parasite.
The single-cell approach measures gene activity cell by cell, rather than averaging expression across all cells in a sample. That allows researchers to examine how different immune-cell populations respond under different conditions. In this analysis, ancestry explained more variation in gene expression than age or sex, according to the preprint.
Genetic differences depended on immune context
Some ancestry-associated expression differences were linked to cis-eQTLs: genetic variants associated with the activity of nearby genes. These accounted for one-quarter of the ancestry-associated differences on average. The authors also found thousands of regulatory variants that were common in the Indigenous South American populations studied but rare or absent in European reference datasets. This highlights how genetic resources drawn from a narrower set of populations can leave some immune regulation less well characterised.
The team also combined eQTL findings with genome-wide association study results. This identified disease-associated regulatory variants whose signals differed by stimulation condition, and an enrichment of ancestry-associated expression differences among genes with colocalizing signals. Colocalization can point to a shared genetic signal behind gene expression and a disease association, making these genes candidates for further study.
The findings describe genetic and molecular associations across measured immune conditions; they are not clinical outcomes for participants. The report is a preprint and has not been peer reviewed.