Evidence that putative ADHD low risk alleles at <I>SNAP25</I> may increase the risk of schizophrenia Export

@article{citeulike:5868874, 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 \&gt; 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. {\copyright} 2009 Wiley-Liss, Inc.}, address = {Department of Psychological Medicine, School of Medicine, Cardiff University, Henry Wellcome Building for Biomedical Research in Wales, Heath Park, Cardiff, UK}, author = {Carroll, L. S. and Kendall, K. and O'Donovan, M. C. and Owen, M. J. and Williams, N. M.}, citeulike-article-id = {5868874}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/ajmg.b.30915}, citeulike-linkout-1 = {http://www3.interscience.wiley.com/cgi-bin/abstract/121632771/ABSTRACT}, doi = {10.1002/ajmg.b.30915}, issn = {1552-485X}, journal = {American Journal of Medical Genetics Part B: Neuropsychiatric Genetics}, keywords = {adhd, assoc, humgen, schizophrenia, synaptic}, number = {7}, pages = {893--899}, posted-at = {2009-10-01 17:11:48}, priority = {2}, title = {Evidence that putative ADHD low risk alleles at <I>SNAP25</I> may increase the risk of schizophrenia}, url = {http://dx.doi.org/10.1002/ajmg.b.30915}, volume = {150B}, year = {2009} }

TY - JOUR ID - citeulike:5868874 L3 - citeulike-article-id:5868874 N2 - 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 &gt; 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. © 2009 Wiley-Liss, Inc. IS - 7 JF - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics SN - 1552-485X AD - Department of Psychological Medicine, School of Medicine, Cardiff University, Henry Wellcome Building for Biomedical Research in Wales, Heath Park, Cardiff, UK EP - 899 TI - Evidence that putative ADHD low risk alleles at <I>SNAP25</I> may increase the risk of schizophrenia VL - 150B SP - 893 KW - adhd KW - assoc KW - humgen KW - schizophrenia KW - synaptic AU - Carroll, LS AU - Kendall, K AU - O'Donovan, MC AU - Owen, MJ AU - Williams, NM PY - 2009/// UR - http://dx.doi.org/10.1002/ajmg.b.30915 ER -