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PMID: 21251332 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines.

Genome biology ·Vol. 12 ·No. 1 ·2011-00-00 ·Pages R10

Bell JT, Pai AA, Pickrell JK, Gaffney DJ, Pique-Regi R, Degner JF, Gilad Y, Pritchard JK

Abstract

DNA methylation is an essential epigenetic mechanism involved in gene regulation and disease, but little is known about the mechanisms underlying inter-individual variation in methylation profiles. Here we measured methylation levels at 22,290 CpG dinucleotides in lymphoblastoid cell lines from 77 HapMap Yoruba individuals, for which genome-wide gene expression and genotype data were also available. Association analyses of methylation levels with more than three million common single nucleotide polymorphisms (SNPs) identified 180 CpG-sites in 173 genes that were associated with nearby SNPs (putatively in cis, usually within 5 kb) at a false discovery rate of 10%. The most intriguing trans signal was obtained for SNP rs10876043 in the disco-interacting protein 2 homolog B gene (DIP2B, previously postulated to play a role in DNA methylation), that had a genome-wide significant association with the first principal component of patterns of methylation; however, we found only modest signal of trans-acting associations overall. As expected, we found significant negative correlations between promoter methylation and gene expression levels measured by RNA-sequencing across genes. Finally, there was a significant overlap of SNPs that were associated with both methylation and gene expression levels. Our results demonstrate a strong genetic component to inter-individual variation in DNA methylation profiles. Furthermore, there was an enrichment of SNPs that affect both methylation and gene expression, providing evidence for shared mechanisms in a fraction of genes.

MeSH Terms
Cell Line DNA Methylation Epigenesis, Genetic Gene Expression Regulation Genome, Human Genome-Wide Association Study Genotype HapMap Project Histones/metabolism Humans Polymorphism, Single Nucleotide Promoter Regions, Genetic Quantitative Trait Loci Transcription, Genetic
Chemicals
Histones
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Bell Jordana T
Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA. jordana@well.ox.ac.uk
Pai Athma A
Pickrell Joseph K
Gaffney Daniel J
Pique-Regi Roger
Degner Jacob F
Gilad Yoav
Pritchard Jonathan K
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Article Info
Journal
Genome biology
Abbr.
Genome Biol
ISSN
1474-760X
DOI
10.1186/gb-2011-12-1-r10
Email
jordana@well.ox.ac.uk
Published
2011-00-00
Epub
2011-00-20
Pages
R10
Language
English
Region
England
NLM ID
100960660
PMCID
PMC3091299
Subset
IM
Grants
NIGMS NIH HHS · GM077959 · United States
Howard Hughes Medical Institute · United States
NIMH NIH HHS · R01 MH084703-01 · United States
NIGMS NIH HHS · T 532 GM007197-34 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1186/gb-2011-12-1-r10 PMC Full Text View journal details
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