期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-017-01586-1
关键词
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资金
- Wellcome Trust [081878/Z/06/Z]
- European Community's Seventh Framework Programme (FP7)
- National Institute for Health Research (NIHR)
- King's College London
- European Research Council [250157]
- BGI
- MRC Lifecourse Epidemiology Unit
- EpiGen Global Research Consortium
- Wellcome Trust [081878/Z/06/Z] Funding Source: Wellcome Trust
- MRC [MC_UP_A620_1017, MC_UU_12011/4] Funding Source: UKRI
- European Research Council (ERC) [250157] Funding Source: European Research Council (ERC)
Integrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites (TFBSs) strongly encoding the DNA methylome. Therefore, genetic polymorphism impacts on the observed epigenome. Furthermore, large genetic variants alter epigenetic signal dosage. Here, we identify DNA methylation variability between GWAS-SNP risk and non-risk haplotypes. In three subsets comprising 3128 MeDIPseq peripheral-blood DNA methylomes, we find 7173 consistent and functionally enriched Differentially Methylated Regions. 36.8% can be attributed to common non-SNP genetic variants. CpG-SNPs, as well as facilitative TFBS-motifs, are also enriched. Highlighting their functional potential, CpG-SNPs strongly associate with allele-specific DNase-I hypersensitivity sites. Our results demonstrate strong DNA methylation allelic differences driven by obligatory or facilitative genetic effects, with potential direct or regional diseaserelated repercussions. These allelic variations require disentangling from pure tissue-specific modifications, may influence array studies, and imply underestimated population variability in current reference epigenomes.
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