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No association between tagging SNPs of SNARE complex genes (STX1A, VAMP2 and SNAP25) and schizophrenia in a Japanese population

Abnormalities in neural connections and the neurotransmitter system appear to be involved in the pathophysiology of schizophrenia. The soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) complex, which consists of Syntaxin1A, vesicle‐associated membrane protein 2 (VAMP2) and synaptosomal‐associated protein 25 kDa (SNAP25), plays an important role in the neurotransmitter system, and is therefore an attractive place to search for candidate genes for schizophrenia. We conducted a two‐stage genetic association analysis of Syntaxin1A (STX1A), VAMP2 and SNAP25 genes with schizophrenia (first‐set screening samples: 377 cases and 377 controls, second‐set confirmation samples: 657 cases and 527 controls). Based on the linkage disequilibrium, 40 SNPs (STX1A, 8 SNPs; VAMP2, 3 SNPs; SNAP25, 29 SNPs) were selected as ‘tagging SNPs’. Only nominally significant associations of an SNP (rs12626080) and haplotype (rs363014 and rs12626080) in SNAP25 were detected in the first‐set screening scan. To validate this significance, we carried out a replication analysis of these SNP and haplotype associations in second‐set samples with a denser set of markers (including five additional SNPs). However, these associations could not be confirmed in the second‐set analysis. These results suggest that the SNARE complex‐related genes do not play a major role in susceptibility to schizophrenia in the Japanese population. © 2008 Wiley‐Liss, Inc.