Incorporating local ancestry improves identification of ancestry-associated methylation signatures and meQTLs in African Americans

Boyang Li, Bradley E. Aouizerat, Youshu Cheng, Kathryn Anastos, Amy C. Justice, Hongyu Zhao, Ke Xu

Research output: Contribution to journalArticlepeer-review

Abstract

Here we report three epigenome-wide association studies (EWAS) of DNA methylation on self-reported race, global genetic ancestry, and local genetic ancestry in admixed Americans from three sets of samples, including internal and external replications (Ntotal = 1224). Our EWAS on local ancestry (LA) identified the largest number of ancestry-associated DNA methylation sites and also featured the highest replication rate. Furthermore, by incorporating ancestry origins of genetic variations, we identified 36 methylation quantitative trait loci (meQTL) clumps for LA-associated CpGs that cannot be captured by a model that assumes identical genetic effects across ancestry origins. Lead SNPs at 152 meQTL clumps had significantly different genetic effects in the context of an African or European ancestry background. Local ancestry information enables superior capture of ancestry-associated methylation signatures and identification of ancestry-specific genetic effects on DNA methylation. These findings highlight the importance of incorporating local ancestry for EWAS in admixed samples from multi-ancestry cohorts.

Original languageEnglish (US)
Pages (from-to)401
Number of pages1
JournalCommunications Biology
Volume5
Issue number1
DOIs
StatePublished - Apr 29 2022

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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