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Behav Brain Funct. 2012 Jun 12;8:31. doi: 10.1186/1744-9081-8-31.

A genetic association study of DNA methylation levels in the DRD4 gene region finds associations with nearby SNPs.

Author information

1
King's College London, MRC Social, Genetic and Developmental Psychiatry Centre,, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. sophia.docherty@iop.kcl.ac.uk

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, rs11246228 and 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 associations. DRD4 has been implicated in several psychiatric disease phenotypes and our results shed light upon the possible mode of action of SNP associations in this region.

PMID:
22691691
PMCID:
PMC3538530
DOI:
10.1186/1744-9081-8-31
[Indexed for MEDLINE]
Free PMC Article

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