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

Jordana T Bell13*, Athma A Pai1, Joseph K Pickrell1, Daniel J Gaffney12, Roger Pique-Regi1, Jacob F Degner1, Yoav Gilad1* and Jonathan K Pritchard12*

Author affiliations

1 Department of Human Genetics, The University of Chicago, 920 E. 58th St, Chicago, IL 60637, USA

2 Howard Hughes Medical Institute, The University of Chicago, 920 E. 58th St, Chicago, IL 60637, USA

3 Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK

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Citation and License

Genome Biology 2011, 12:R10  doi:10.1186/gb-2011-12-1-r10

Published: 20 January 2011



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.