African Americans (AAs) are an admixed population with widely varying proportion of West African ancestry (WAA). Here we report the correlation of WAA to gene expression and DNA methylation in AA-derived hepatocytes, a cell type important in disease and drug response. We perform mediation analysis to test whether methylation is a mediator of the effect of ancestry on expression. GTEx samples and a second cohort are used as validation. One hundred and thirty-one genes are associated with WAA (FDR < 0.10), 28 of which replicate and represent 220 GWAS phenotypes. Among PharmGKB pharmacogenes, VDR, PTGIS, ALDH1A1, CYP2C19, and P2RY1 nominally associate with WAA (p < 0.05). We find 1037 WAA-associated, differentially methylated regions (FDR < 0.05), with hypomethylated genes enriched in drug-response pathways. In conclusion, WAA contributes to variability in hepatocyte expression and DNA methylation with identified genes previously implicated for diseases disproportionately affecting AAs, including cardiovascular (PTGIS, PLAT) and renal (APOL1) disease, and drug response (CYP2C19).

中文翻译：

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非洲裔美国人的肝细胞基因表达和DNA甲基化是祖先依赖的机制。

非裔美国人（AAs）是混血人口，其西非血统（WAA）的比例差异很大。在这里，我们报告了WAA与AA衍生的肝细胞（一种在疾病和药物反应中很重要的细胞类型）中的基因表达和DNA甲基化的相关性。我们进行中介分析以测试甲基化是否是祖先对表达的影响的中介。GTEx样本和第二个队列用作验证。131个基因与WAA相关（FDR <0.10），其中28个基因复制并代表220个GWAS表型。在PharmGKB药物基因中，VDR，PTGIS，ALDH1A1，CYP2C19和P2RY1标称与WAA相关（p <0.05）。我们发现1037 WAA相关，差异甲基化的区域（FDR <0.05），与低甲基化的基因丰富了药物反应途径。综上所述，