Research output: Contribution to journal › Article › peer-review
Christopher G Bell, Fei Gao, Wei Yuan, Leonie Roos, Richard J Acton, Yudong Xia, Jordana Bell, Kirsten Ward, Massimo Mangino, Pirro G Hysi, Jun Wang, Timothy D Spector
Original language | English |
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Article number | 8 |
Journal | Nature Communications |
Volume | 9 |
Early online date | 2 Jan 2018 |
DOIs | |
Accepted/In press | 29 Sep 2017 |
E-pub ahead of print | 2 Jan 2018 |
Published | 1 Dec 2018 |
Obligatory and facilitative allelic_BELL_Published2January2018_GOLD VoR (CC BY)
Obligatory_and_facilitative_allelic_BELL_Published2January2018_GOLD_VoR_CC_BY_.pdf, 1.53 MB, application/pdf
Uploaded date:15 Jan 2018
Version:Final published version
Licence:CC BY
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 MeDIP-seq 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 disease-related 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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