Genetic control of DNA methylation is largely shared across European and East Asian populations

Alesha A. Hatton, Fei-Fei Cheng, Tian Lin, Ren-Juan Shen, Jie Chen, Zhili Zheng, Jia Qu, Fan Lyu, Sarah E. Harris, Simon R. Cox, Zi-Bing Jin, Nicholas G. Martin, Dongsheng Fan, Grant W. Montgomery, Jian Yang, Naomi R. Wray, Riccardo E. Marioni, Peter M. Visscher and Allan F. McRae ()
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Alesha A. Hatton: The University of Queensland
Fei-Fei Cheng: The University of Queensland
Tian Lin: The University of Queensland
Ren-Juan Shen: Capital Medical University
Jie Chen: Wenzhou Medical University
Zhili Zheng: The University of Queensland
Jia Qu: Wenzhou Medical University
Fan Lyu: Wenzhou Medical University
Sarah E. Harris: University of Edinburgh
Simon R. Cox: University of Edinburgh
Zi-Bing Jin: Capital Medical University
Nicholas G. Martin: Queensland Institute of Medical Research Berghofer
Dongsheng Fan: Peking University Third Hospital
Grant W. Montgomery: The University of Queensland
Jian Yang: Westlake University
Naomi R. Wray: The University of Queensland
Riccardo E. Marioni: University of Edinburgh
Peter M. Visscher: The University of Queensland
Allan F. McRae: The University of Queensland

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-47005-0

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