Evidence that putative ADHD low risk alleles at SNAP25 may increase the risk of schizophrenia.

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 (r(2) > 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.

• Authors: L S Carroll, K Kendall, M C O'Donovan, M J Owen, N M Williams
• Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 150B Issue 7 Pg. 893-9 (Oct 05 2009) ISSN: 1552-485X [Electronic] United States
• PMID: 19132710 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2009 Wiley-Liss, Inc.

Chemical References

• Synaptosomal-Associated Protein 25

Topics

• Alleles
• Attention Deficit Disorder with Hyperactivity (complications, genetics)
• DNA Mutational Analysis
• Female
• Genetic Predisposition to Disease
• Genome, Human (genetics)
• Humans
• Male
• Polymorphism, Single Nucleotide (genetics)
• Schizophrenia (complications, genetics)
• Synaptosomal-Associated Protein 25 (genetics)