@article{a49ba5bc40aa43b88df6880ddd7763a7,
title = "Genetic control of DNA methylation is largely shared across European and East Asian populations",
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.",
keywords = "DNA methylation, epigenomics, genome-wide association studies",
author = "Alesha Hatton and Fei-Fei Cheng and Tian Lin and Ren-Juan Shen and Jie Chen and Zhili Zheng and Jia Qu and Fan Lyu and Harris, {Sarah E.} and Cox, {Simon R.} and Zi-Bing Jin and Nicholas Martin and Dongsheng Fan and Grant Montgomery and Jian Yang and Naomi Wray and Marioni, {Riccardo E.} and Peter Visscher and Allan Mcrae",
note = "The mQTL summary data from the meta-analysis of samples of each European (n = 3071) and East Asian (n = 2099) ancestry generated in this study are available at https://yanglab.westlake.edu.cn/software/smr/#mQTLsummarydata. These results have been provided in SMR BESD format (see https://yanglab.westlake.edu.cn/software/smr/#BESDformat). Access to individual level data for each of the cohorts is as follows: The SGPD DNAm data are available from the Gene Expression Omnibus (GEO) under accession code GSE145361. The LBC DNAm data are available at the European Genome-phenome Archive under accession number EGAS00001000910. DNAm data for the BSGS are available from the Gene Expression Omnibus under accession code GSE56105. Deposit of CHNMND DNAm data in a repository does not comply with the consent process and ethics approval, but sharing data is possible by emailing the corresponding author of the cohort publication. Primary data of the Tibetan and Han Chinese subjects are available through application at https://www.wmubiobank.org. Analysis of the UK Biobank resource was conducted under the application number 12505. The genotype and phenotype data are available upon application to the UKB (http://www.ukbiobank.ac.uk/). Health and Retirement Study data were accessed from dbGaP (accessions: phs000428). The web links for the publicly available datasets used in the study are as follows: The 1000 Genomes Phase 3 data available at https://ftp.1000genomes.ebi.ac.uk/vol1/ftp/phase3/; mQTL data from Hawe et al.31: https://zenodo.org/record/5196216#.YRZ3TfJxeUk; mQTL data from Min et al.83 data: http://mqtldb.godmc.org.uk; GWAS summary statistics for 220 traits used for SMR from Sakaue et al.41: https://pheweb.jp/downloads; Annotation of Infinium DNA Methylation BeadChip probes: https://zwdzwd.github.io/InfiniumAnnotation. Code availability The publicly available software tools used for data analysis are described in the “Methods” with the web links as follows: plink (v2.0): https://www.cog-genomics.org/plink/2.0; OSCA (v0.46): https://yanglab.westlake.edu.cn/software/osca; GCTA (v1.93.2beta): https://yanglab.westlake.edu.cn/software/gcta/#Overview; susieR: https://stephenslab.github.io/susieR; susieX: https://github.com/getian107/SuSiEx; SMR (v1.03): https://yanglab.westlake.edu.cn/software/smr/.",
year = "2024",
doi = "10.1038/s41467-024-47005-0",
language = "English",
volume = "15",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}