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

Author

Listed:
  • Alesha A. Hatton

    (The University of Queensland)

  • Fei-Fei Cheng

    (The University of Queensland
    Westlake University)

  • Tian Lin

    (The University of Queensland)

  • Ren-Juan Shen

    (Capital Medical University
    Wenzhou 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
    Wenzhou 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
    Westlake Laboratory of Life Sciences and Biomedicine)

  • Naomi R. Wray

    (The University of Queensland
    The University of Queensland)

  • Riccardo E. Marioni

    (University of Edinburgh)

  • Peter M. Visscher

    (The University of Queensland)

  • Allan F. McRae

    (The University of Queensland)

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.

Suggested Citation

  • 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. M, 2024. "Genetic control of DNA methylation is largely shared across European and East Asian populations," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47005-0
    DOI: 10.1038/s41467-024-47005-0
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