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Possible association of the semaphorin 3D gene (SEMA3D) with schizophrenia.

Abstract
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.
AuthorsTakashi Fujii, Hirofumi Uchiyama, Noriko Yamamoto, Hiroaki Hori, Masahiko Tatsumi, Masanori Ishikawa, Kunimasa Arima, Teruhiko Higuchi, Hiroshi Kunugi
JournalJournal of psychiatric research (J Psychiatr Res) Vol. 45 Issue 1 Pg. 47-53 (Jan 2011) ISSN: 1879-1379 [Electronic] England
PMID20684831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Ltd. All rights reserved.
Chemical References
  • Semaphorins
Topics
  • Adult
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease (genetics)
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide (genetics)
  • Schizophrenia (genetics)
  • Semaphorins (genetics)

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