Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci

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 and Timothy D. Spector
Additional contact information
Christopher G. Bell: King’s College London
Fei Gao: BGI-Shenzhen
Wei Yuan: King’s College London
Leonie Roos: King’s College London
Richard J. Acton: University of Southampton
Yudong Xia: BGI-Shenzhen
Jordana Bell: King’s College London
Kirsten Ward: King’s College London
Massimo Mangino: King’s College London
Pirro G. Hysi: King’s College London
Jun Wang: University of Southampton
Timothy D. Spector: King’s College London

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-01586-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-01586-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-01586-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().