We 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.

我们利用 2,733 名非裔美国人、波多黎各人和墨西哥裔美国人的全基因组和 RNA 测序数据，探索了全血基因表达遗传结构中与祖先相关的差异。我们发现，基因表达的遗传力随着非洲遗传血统比例的增加而显着增加，而随着美洲原住民血统比例的增加而降低，反映了杂合性和遗传方差之间的关系。在可遗传的蛋白质编码基因中，非洲血统中祖先特异性表达数量性状基因座 (anc-eQTL) 的流行率为 30%，美洲原住民血统中的流行率为 8%。大多数 anc-eQTL (89%) 是由等位基因频率的群体差异驱动的。使用在我们的混合群体中训练的转录组预测模型，对 28 个性状的多祖先汇总统计进行转录组范围的关联分析，发现比使用基因型组织表达项目的数据训练的模型多 79% 的基因-性状关联。我们的研究强调了测量大型且祖先多样化人群的基因表达对于实现新发现和减少差异的重要性。