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Behavioral and Brain Functions

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Open Access 01-12-2012 | Research

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

Authors: Sophia J. Docherty, Oliver S. P. Davis, Claire M. A. Haworth, Robert Plomin, Ursula D’Souza, Jonathan Mill

Published in: Behavioral and Brain Functions | Issue 1/2012

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.

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Title: A genetic association study of DNA methylation levels in the DRD4 gene region finds associations with nearby SNPs
Authors: Sophia J. Docherty
Oliver S. P. Davis
Claire M. A. Haworth
Robert Plomin
Ursula D’Souza
Jonathan Mill
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Behavioral and Brain Functions / Issue 1/2012
Electronic ISSN: 1744-9081
DOI: https://doi.org/10.1186/1744-9081-8-31

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

ABSTRACT

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

ABSTRACT

Background

Methods

Results

Conclusions

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