DNA variation in the SNAP25 gene confers risk to ADHD and is associated with reduced expression in prefrontal cortex
Abstract
Background: The Coloboma mouse carries a similar to 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 postmortem tissue derived from the inferior frontal gyrus of 89 unaffected adults. Significant associations with the A allele of SNP rs362990 (chi(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.
Citation
Hawi , Z , Matthews , N , Wagner , J , Wallace , R H , Butler , T J , Vance , A , Kent , L , Gill , M & Bellgrove , M A 2013 , ' DNA variation in the SNAP25 gene confers risk to ADHD and is associated with reduced expression in prefrontal cortex ' , PLoS ONE , vol. 8 , no. 4 , e60274 . https://doi.org/10.1371/journal.pone.0060274
Publication
PLoS ONE
Status
Peer reviewed
ISSN
1932-6203Type
Journal article
Description
This work was part funded by the MRC.Collections
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