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纳入当地血统可提高非洲裔美国人中与血统相关的甲基化特征和 meQTL 的鉴定。

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

机构信息

Department of Biostatistics, School of Public Health, Yale University, New Haven, CT, United States.

VA Connecticut Healthcare System, US Department of Veterans Affairs, West Haven, CT, United States.

出版信息

Commun Biol. 2022 Apr 29;5(1):401. doi: 10.1038/s42003-022-03353-5.

DOI:10.1038/s42003-022-03353-5
PMID:35488087
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9054854/
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 (N= 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.

摘要

在这里，我们报告了三项关于自我报告的种族、全球遗传血统和混合美国人局部遗传血统的 DNA 甲基化的全基因组关联研究（EWAS），这些研究基于三组样本，包括内部和外部重复（N=1224）。我们关于局部血统（LA）的 EWAS 鉴定出了数量最多的与血统相关的 DNA 甲基化位点，并且复制率也最高。此外，通过整合遗传变异的血统起源，我们鉴定出了 36 个与 LA 相关的 CpG 相关的甲基化数量性状基因座（meQTL）簇，这些簇不能通过假设在不同的血统起源中具有相同的遗传效应的模型来捕获。152 个 meQTL 簇中的主要 SNP 在非洲或欧洲血统背景下具有显著不同的遗传效应。局部血统信息能够更好地捕捉与血统相关的甲基化特征，并确定 DNA 甲基化中与血统相关的特定遗传效应。这些发现强调了在多血统队列的混合样本中纳入局部血统进行 EWAS 的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03ae/9054854/2692472b0a1d/42003_2022_3353_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03ae/9054854/a54012e12aa4/42003_2022_3353_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03ae/9054854/2e9a3cceb63b/42003_2022_3353_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03ae/9054854/2692472b0a1d/42003_2022_3353_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03ae/9054854/a54012e12aa4/42003_2022_3353_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03ae/9054854/1e2251e60d83/42003_2022_3353_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03ae/9054854/f2401472e2f8/42003_2022_3353_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03ae/9054854/2e9a3cceb63b/42003_2022_3353_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03ae/9054854/2692472b0a1d/42003_2022_3353_Fig5_HTML.jpg

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