Abstract
AbstractWe explored ancestry-related differences in the genetic architecture of whole-blood gene expression using whole-genome and RNA sequencing data from 2,733 African Americans, Puerto Ricans and Mexican Americans. We found that heritability of gene expression significantly increased with greater proportions of African genetic ancestry and decreased with higher proportions of Indigenous American ancestry, reflecting the relationship between heterozygosity and genetic variance. Among heritable protein-coding genes, the prevalence of ancestry-specific expression quantitative trait loci (anc-eQTLs) was 30% in African ancestry and 8% for Indigenous American ancestry segments. Most anc-eQTLs (89%) were driven by population differences in allele frequency. Transcriptome-wide association analyses of multi-ancestry summary statistics for 28 traits identified 79% more gene–trait associations using transcriptome prediction models trained in our admixed population than models trained using data from the Genotype-Tissue Expression project. Our study highlights the importance of measuring gene expression across large and ancestrally diverse populations for enabling new discoveries and reducing disparities.
Funder
U.S. Department of Health & Human Services | NIH | National Cancer Institute
U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute
U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences
Publisher
Springer Science and Business Media LLC
Cited by
7 articles.
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