Journal
JOURNAL OF PSYCHIATRIC RESEARCH
Volume 45, Issue 1, Pages 47-53Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jpsychires.2010.05.004
Keywords
Semaphorin; Plexin; Non-synonymous polymorphism; Schizophrenia; Haplotype
Categories
Funding
- Japan Society for the Promotion of Science (JSPS)
- Japan Human Sciences Foundation
- Health and Labor Sciences Research Grants
- Japan Health Sciences Foundation
- National Institute of Biomedical Innovation (NIBIO)
- JST, CREST
- Ministry of Education, Culture, Sports, Science and Technology of Japan
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Semaphorins are ligands of plexins, and the plexin semaphorin signaling system is widely involved in many neuronal events including axon guidance, cell migration, axon pruning, and synaptic plasticity. The plexin A2 gene (PLXNA2) has been reported to be associated with schizophrenia. This finding prompted us to examine the possible association between the semaphorin 3D gene (SEMA3D) and schizophrenia in a Japanese population. We genotyped 9 tagging single nucleotide polymorphisms (SNPs) of SEMA3D including a non-synonymous variation, Lys701Gln (rs7800072), in a sample of 506 patients with schizophrenia and 941 healthy control subjects. The Gln701 allele showed a significant protective effect against the development of schizophrenia (p = 0.0069, odds ratio = 0.76, 95% confidence interval 0.63 to 0.93). Furthermore, the haplotype-based analyses revealed a significant association. The four-marker analysis (rs2190208-rs1029564-rs17159614-rs12176601), in particular, not including the Lys701Gln, revealed a highly significant association (p = 0.00001, global permutation), suggesting that there may be other functional polymorphisms within SEMA3D. Our findings provide strong evidence that SEMA3D confers susceptibility to schizophrenia, which could contribute to the neurodevelopmental impairments in the disorder. (C) 2010 Elsevier Ltd. All rights reserved.
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