美国加州大学Elad Ziv、Esteban González Burchard和科罗拉多大学Christopher R. Gignoux研究团队合作取得一项新成果。经过不懈努力，他们通过对非洲裔美国人、波多黎各人和墨西哥裔美国人的基因表达分析揭示了祖先特异性遗传结构。相关论文于2023年5月25日发表于国际学术期刊《自然—遗传学》杂志。

研究人员通过对2733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测序数据进行分析，探索了全血基因表达遗传结构中与祖先相关的差异。研究发现，基因表达的遗传能力随着非洲遗传血统比例的增加而显著增加，随着美洲原住民血统比例的增加而降低，这反映了杂合性与遗传变异之间的关系。在可遗传的蛋白质编码基因中，祖先特异性表达数量性状位点（anc-eQTLs）的患病率在非洲血统中为30%，而在美洲土著血统中为8%。大多数anc-eQTLs（89）是由群体等位基因频率差异造成的。

使用该研究提供的方法对转录组预测模型进行数据校准，在对28个性状进行的多血统汇总统计时，比使用基因型-组织表达项目进行数据校准的模型多发现了79%的基因-性状关联。该研究强调在对基因表达进行测量时，分析大样本量和祖先多样化人群对于实现新发现和减少差异的重要性。

附：英文原文

Title: Gene expression in African Americans, Puerto Ricans and Mexican Americans reveals ancestry-specific patterns of genetic architecture

Author: Kachuri, Linda, Mak, Angel C. Y., Hu, Donglei, Eng, Celeste, Huntsman, Scott, Elhawary, Jennifer R., Gupta, Namrata, Gabriel, Stacey, Xiao, Shujie, Keys, Kevin L., Oni-Orisan, Akinyemi, Rodrguez-Santana, Jos R., LeNoir, Michael A., Borrell, Luisa N., Zaitlen, Noah A., Williams, L. Keoki, Gignoux, Christopher R., Burchard, Esteban Gonzlez, Ziv, Elad

Issue&Volume: 2023-05-25

Abstract: 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.

DOI: 10.1038/s41588-023-01377-z

Source: https://www.nature.com/articles/s41588-023-01377-z