TY - JOUR
T1 - Incorporating local ancestry improves identification of ancestry-associated methylation signatures and meQTLs in African Americans
AU - Li, Boyang
AU - Aouizerat, Bradley E.
AU - Cheng, Youshu
AU - Anastos, Kathryn
AU - Justice, Amy C.
AU - Zhao, Hongyu
AU - Xu, Ke
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s42003-022-03353-5
DO - 10.1038/s42003-022-03353-5
M3 - Article
C2 - 35488087
AN - SCOPUS:85129219752
SN - 2399-3642
VL - 5
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 401
ER -