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PLoS One. 2013 Apr 12;8(4):e60274. doi: 10.1371/journal.pone.0060274. Print 2013.

DNA variation in the SNAP25 gene confers risk to ADHD and is associated with reduced expression in prefrontal cortex.

Author information

1
Queensland Brain Institute, the University of Queensland, Brisbane, Australia. z.hawi@uq.edu.au

Abstract

BACKGROUND:

The Coloboma mouse carries a ∼2 cM deletion encompassing the SNAP25 gene and has a hyperactive phenotype similar to that of ADHD. Such mice are 3 fold more active compared to their control littermates. Genetic association studies support a role for allelic variants of the human SNAP25 gene in predisposing to ADHD.

METHODS/PRINCIPAL FINDINGS:

We performed association analysis across the SNAP25 gene in 1,107 individuals (339 ADHD trios). To assess the functional relevance of the SNAP25-ADHD associated allele, we performed quantitative PCR on post-mortem tissue derived from the inferior frontal gyrus of 89 unaffected adults. Significant associations with the A allele of SNP rs362990 (χ(2) = 10, p-corrected = 0.019, OR = 1.5) and three marker haplotypes (rs6108461, rs362990 and rs362998) were observed. Furthermore, a significant additive decrease in the expression of the SNAP25 transcript as a function of the risk allele was also observed. This effect was detected at the haplotype level, where increasing copies of the ADHD-associated haplotype reduced the expression of the transcript.

CONCLUSIONS:

Our data show that DNA variation at SNAP25 confers risk to ADHD and reduces the expression of the transcript in a region of the brain that is critical for the regulation of attention and inhibition.

PMID:
23593184
PMCID:
PMC3625226
DOI:
10.1371/journal.pone.0060274
[Indexed for MEDLINE]
Free PMC Article

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