a genetic association study of dna methylation levels in the drd4 gene region finds associations with nearby snps基因关联研究dna甲基化水平的drd4基因区域发现对附近的snp.pdfVIP

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a genetic association study of dna methylation levels in the drd4 gene region finds associations with nearby snps基因关联研究dna甲基化水平的drd4基因区域发现对附近的snp.pdf

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a genetic association study of dna methylation levels in the drd4 gene region finds associations with nearby snps基因关联研究dna甲基化水平的drd4基因区域发现对附近的snp

Docherty et al. Behavioral and Brain Functions 2012, 8:31 /content/8/1/31 RESEARCH Open Access A genetic association study of DNA methylation levels in the DRD4 gene region finds associations with nearby SNPs * Sophia J Docherty , Oliver SP Davis, Claire MA Haworth, Robert Plomin, Ursula D’Souza and Jonathan Mill ABSTRACT Background: Dopamine receptor D4 (DRD4) polymorphisms have been associated with a number of psychiatric disorders, but little is known about the mechanism of these associations. DNA methylation is linked to the regulation of gene expression and plays a vital role in normal cellular function, with abnormal DNA methylation patterns implicated in a range of disorders. Recent evidence suggests DNA methylation can be influenced by cis-acting DNA sequence variation, that is, DNA sequence variation located nearby on the same chromosome. Methods: To investigate the potential influence of cis-acting genetic elements within DRD4, we analysed DRD4 promoter DNA methylation levels in the transformed lymphoblastoid cell-line DNA of 89 individuals (from 30 family-trios). Five SNPs located +/−10kb of the promoter region were interrogated for associations with DNA methylation levels. Results: Four significant SNP associations were found with DNA methylation (rs3758653, rs752306, rand rs936465). The associations of rs3758653 and rs936465 with DNA methylation were tested and nominally replicated (p-value 0.05) in post-mortem brain tissue from an independent sample (N = 18). Interestingly, the DNA methylation patterns observed in post-mortem brain tissue were similar to those observed in transformed lymphoblastoid cell line DNA. Conclusions: The link reported between DNA sequence and DNA methylation offers a possible functional role to seemingly non-functional SNP asso