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

Hawi, Ziarih, Matthews, Natasha, Wagner, Joseph, Wallace, Robyn H., Butler, Tim J., Vance, Alasdair, Kent, Lindsey, Gill, Michael and Bellgrove, Mark A. (2013) DNA variation in the SNAP25 gene confers risk to ADHD and is associated with reduced expression in prefrontal cortex. PLoS One, 8 4: e60274.1-e60274.8. doi:10.1371/journal.pone.0060274


Author Hawi, Ziarih
Matthews, Natasha
Wagner, Joseph
Wallace, Robyn H.
Butler, Tim J.
Vance, Alasdair
Kent, Lindsey
Gill, Michael
Bellgrove, Mark A.
Title DNA variation in the SNAP25 gene confers risk to ADHD and is associated with reduced expression in prefrontal cortex
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-04
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0060274
Open Access Status DOI
Volume 8
Issue 4
Start page e60274.1
End page e60274.8
Total pages 8
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2014
Language eng
Formatted 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 (χ2 = 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.
Keyword Deficit Hyperactivity Disorder
Genome wide association
Mouse Mutant Coloboma
Candidate Gene
Snare Complex
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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