Hepatocyte gene expression and DNA methylation as ancestry-dependent mechanisms in African Americans

C. S. Park, T. De, Y. Xu, Y. Zhong, E. Smithberger, C. Alarcon, E. R. Gamazon, M. A. Perera*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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).

Original languageEnglish (US)
Article number29
Journalnpj Genomic Medicine
Volume4
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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