Evidence that putative ADHD low risk alleles atSNAP25may increase the risk of schizophrenia

Carroll, Liam Stuart, Kendall, Kimberley ORCID: https://orcid.org/0000-0002-6755-6121, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 and Williams, Nigel Melville ORCID: https://orcid.org/0000-0003-1177-6931 2009. Evidence that putative ADHD low risk alleles atSNAP25may increase the risk of schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 150B (7) , pp. 893-899. 10.1002/ajmg.b.30915

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Abstract

Synaptosomal Associated Protein 25 kDa (SNAP25) has been implicated in the pathogenesis of schizophrenia by numerous neuropathological studies and genetic variation at SNAP25 has been reported to be associated with ADHD. Expression levels of the putative schizophrenia susceptibility gene DTNBP1 has been shown to influence the levels of SNAP25 in vitro. We undertook directed mutation screening of SNAP25 in UK schizophrenic cases followed by direct association analysis of all variants identified and identified known exonic SNPs that showed evidence for association (rs3746544 P = 0.004 OR = 1.26, rs8636 P = 0.003 OR = 1.27), although these SNPs are highly correlated (r2 > 0.99). We additionally genotyped a further 31 tag SNPs spanning the SNAP25 locus and identified several independent SNPs that were nominally associated with schizophrenia (strongest association at rs3787283, P = 0.006, OR = 1.25) however, due to the number of tests performed no SNP met experiment-wise significance (minimum permuted P-value  = 0.1). Post hoc analysis revealed that the SNPs nominally associated with schizophrenia (rs3787283, rs3746544) were the same as those previously demonstrated to be associated with ADHD but with the opposite alleles, allowing the intriguing hypothesis that genetic variation at SNAP25 may be differentially associated with both schizophrenia and ADHD.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General)
Uncontrolled Keywords:	schizophrenia; ADHD; SNAP25; association
Publisher:	Wiley-Blackwell
ISSN:	1552-4841
Last Modified:	05 Oct 2024 13:55
URI:	https://orca.cardiff.ac.uk/id/eprint/22121

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