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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.date.accessioned2013-08-06T14:31:02Z
dc.date.available2013-08-06T14:31:02Z
dc.date.issued2013-04-12
dc.identifier55104009
dc.identifierfd7960c6-e533-4e53-854a-42a201db4671
dc.identifier000317385300013
dc.identifier84876076939
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 . https://doi.org/10.1371/journal.pone.0060274en
dc.identifier.issn1932-6203
dc.identifier.otherORCID: /0000-0002-5315-3399/work/60195336
dc.identifier.urihttps://hdl.handle.net/10023/3934
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.format.extent8
dc.format.extent468934
dc.language.isoeng
dc.relation.ispartofPLoS ONEen
dc.subjectSNAP-25 geneen
dc.subjectGenome-wide associationen
dc.subjectCandidate geneen
dc.subjectSusceptibilityen
dc.subjectSnare complexen
dc.subjectDeficit hyperactivity disorderen
dc.subjectMouse mutant colobomaen
dc.subjectPolymorphismsen
dc.subjectR Medicineen
dc.subject.lccRen
dc.titleDNA variation in the SNAP25 gene confers risk to ADHD and is associated with reduced expression in prefrontal cortexen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.identifier.doi10.1371/journal.pone.0060274
dc.description.statusPeer revieweden


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