Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
School of Life Sciences, Westlake University, Hangzhou, 310030, Zhejiang, China.
Nat Commun. 2024 Mar 28;15(1):2713. doi: 10.1038/s41467-024-47005-0.
DNA methylation is an ideal trait to study the extent of the shared genetic control across ancestries, effectively providing hundreds of thousands of model molecular traits with large QTL effect sizes. We investigate cis DNAm QTLs in three European (n = 3701) and two East Asian (n = 2099) cohorts to quantify the similarities and differences in the genetic architecture across populations. We observe 80,394 associated mQTLs (62.2% of DNAm probes with significant mQTL) to be significant in both ancestries, while 28,925 mQTLs (22.4%) are identified in only a single ancestry. mQTL effect sizes are highly conserved across populations, with differences in mQTL discovery likely due to differences in allele frequency of associated variants and differing linkage disequilibrium between causal variants and assayed SNPs. This study highlights the overall similarity of genetic control across ancestries and the value of ancestral diversity in increasing the power to detect associations and enhancing fine mapping resolution.
DNA 甲基化是研究不同血统之间遗传控制程度的理想特征,它有效地提供了数十万种具有大 QTL 效应大小的模型分子特征。我们在三个欧洲队列(n=3701)和两个东亚队列(n=2099)中研究了顺式 DNAm QTL,以量化人群之间遗传结构的相似性和差异。我们观察到 80394 个相关的 mQTL(62.2%的 DNAm 探针有显著的 mQTL)在两个血统中都是显著的,而 28925 个 mQTL(22.4%)仅在一个血统中被识别。mQTL 效应大小在人群中高度保守,mQTL 发现的差异可能是由于相关变异体的等位基因频率不同,以及因果变异体与检测 SNP 之间的连锁不平衡不同。本研究强调了遗传控制在不同血统之间的总体相似性,以及祖先多样性在增加检测关联的能力和提高精细映射分辨率方面的价值。