title: 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.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujii
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uchiyama
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hori
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tatsumi
authors.forename: Masanori
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Kunimasa
authors.initials: K
authors.lastname: Arima
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Higuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D039961:Semaphorins / Q000235:genetics*
chemical_list: D039961:Semaphorins