期刊
GENOME BIOLOGY
卷 12, 期 1, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/gb-2011-12-1-r10
关键词
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资金
- Sir Henry Wellcome postdoctoral fellowship
- Chicago Fellows Program
- American Heart Association
- Howard Hughes Medical Institute
- National Institutes of Health [T 532 GM007197-34, RO1 MH084703-01, GM077959]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007197, R01GM077959] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH084703] Funding Source: NIH RePORTER
Background: 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. Results: 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. Conclusions: 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.
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