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

• Published in: Genome biology 2011-01, Vol.12 (1), p.R10-R10, Article R10
• Main Authors: Bell, Jordana T, Pai, Athma A, Pickrell, Joseph K, Gaffney, Daniel J, Pique-Regi, Roger, Degner, Jacob F, Gilad, Yoav, Pritchard, Jonathan K
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 1474-760X; 1465-6906; 1474-760X; 1465-6914
• DOI: 10.1186/gb-2011-12-1-r10

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.