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; Allan F McRae

doi:10.1038/s41467-024-47005-0

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

Nat Commun. 2024 Mar 28;15(1):2713. doi: 10.1038/s41467-024-47005-0.

Authors

Alesha A Hatton¹, Fei-Fei Cheng^{1

2}, Tian Lin¹, Ren-Juan Shen^{3

4}, Jie Chen⁴, Zhili Zheng¹, Jia Qu⁴, Fan Lyu⁴, Sarah E Harris⁵, Simon R Cox⁵, Zi-Bing Jin^{3

4}, Nicholas G Martin⁶, Dongsheng Fan⁷, Grant W Montgomery¹, Jian Yang^{2

8}, Naomi R Wray^{1

9}, Riccardo E Marioni¹⁰, Peter M Visscher¹, Allan F McRae¹¹

Affiliations

¹ Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
² School of Life Sciences, Westlake University, Hangzhou, 310030, Zhejiang, China.
³ Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, 100008, Beijing, China.
⁴ School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, 325027, China.
⁵ Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
⁶ Queensland Institute of Medical Research Berghofer, Brisbane, QLD, 4006, Australia.
⁷ Department of Neurology, Peking University Third Hospital, 100191, Beijing, China.
⁸ Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, Zhejiang, China.
⁹ Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia.
¹⁰ Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
¹¹ Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia. a.mcrae@uq.edu.au.

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.

MeSH terms

DNA Methylation* / genetics
East Asian People*
Gene Expression Regulation
Genome-Wide Association Study
Humans
Linkage Disequilibrium
Polymorphism, Single Nucleotide
Quantitative Trait Loci / genetics