Unknown

Dataset Information

0

Allele-specific methylation occurs at genetic variants associated with complex disease.


ABSTRACT: We hypothesize that the phenomenon of allele-specific methylation (ASM) may underlie the phenotypic effects of multiple variants identified by Genome-Wide Association studies (GWAS). We evaluate ASM in a human population and document its genome-wide patterns in an initial screen at up to 380,678 sites within the genome, or up to 5% of the total genomic CpGs. We show that while substantial inter-individual variation exists, 5% of assessed sites show evidence of ASM in at least six samples; the majority of these events (81%) are under genetic influence. Many of these cis-regulated ASM variants are also eQTLs in peripheral blood mononuclear cells and monocytes and/or in high linkage-disequilibrium with variants linked to complex disease. Finally, focusing on autoimmune phenotypes, we extend this initial screen to confirm the association of cis-regulated ASM with multiple complex disease-associated variants in an independent population using next-generation bisulfite sequencing. These four variants are implicated in complex phenotypes such as ulcerative colitis and AIDS progression disease (rs10491434), Celiac disease (rs2762051), Crohn's disease, IgA nephropathy and early-onset inflammatory bowel disease (rs713875) and height (rs6569648). Our results suggest cis-regulated ASM may provide a mechanistic link between the non-coding genetic changes and phenotypic variation observed in these diseases and further suggests a route to integrating DNA methylation status with GWAS results.

SUBMITTER: Hutchinson JN 

PROVIDER: S-EPMC4049588 | BioStudies | 2014-01-01

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC5856270 | BioStudies
2017-01-01 | S-EPMC5477265 | BioStudies
2014-01-01 | S-EPMC4096397 | BioStudies
2018-01-01 | S-EPMC6334214 | BioStudies
2010-01-01 | S-EPMC2820163 | BioStudies
2010-01-01 | S-EPMC2953749 | BioStudies
2014-07-01 | E-GEOD-56298 | ArrayExpress
| GSE56298 | GEO
2019-01-01 | S-EPMC6776507 | BioStudies
2016-01-01 | S-EPMC4863558 | BioStudies