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dc.contributor.authorHawi, Ziarih
dc.contributor.authorMatthews, Natasha
dc.contributor.authorWagner, Joseph
dc.contributor.authorWallace, Robyn H.
dc.contributor.authorButler, Tim J.
dc.contributor.authorVance, Alasdair
dc.contributor.authorKent, Lindsey
dc.contributor.authorGill, Michael
dc.contributor.authorBellgrove, Mark A.
dc.identifier.citationHawi , 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 .
dc.identifier.otherPURE: 55104009
dc.identifier.otherPURE UUID: fd7960c6-e533-4e53-854a-42a201db4671
dc.identifier.otherWOS: 000317385300013
dc.identifier.otherScopus: 84876076939
dc.identifier.otherORCID: /0000-0002-5315-3399/work/60195336
dc.descriptionThis work was part funded by the MRC.en
dc.description.abstractBackground: 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.
dc.relation.ispartofPLoS ONEen
dc.rights© 2013 Hawi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectSNAP-25 geneen
dc.subjectGenome-wide associationen
dc.subjectCandidate geneen
dc.subjectSnare complexen
dc.subjectDeficit hyperactivity disorderen
dc.subjectMouse mutant colobomaen
dc.subjectR Medicineen
dc.titleDNA variation in the SNAP25 gene confers risk to ADHD and is associated with reduced expression in prefrontal cortexen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.description.statusPeer revieweden

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