Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia

Mah, S., Nelson, M. R., DeLisi, L. E., Reneland, R. H., Markward, N., James, M. R., Nyholt, D. R., Hayward, N., Handoko, H., Mowry, B., Kammerer, S. and Braun, A. (2006) Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia. Molecular Psychiatry, 11 5: 471-478. doi:10.1038/

Author Mah, S.
Nelson, M. R.
DeLisi, L. E.
Reneland, R. H.
Markward, N.
James, M. R.
Nyholt, D. R.
Hayward, N.
Handoko, H.
Mowry, B.
Kammerer, S.
Braun, A.
Title Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1359-4184
Publication date 2006
Sub-type Article (original research)
DOI 10.1038/
Volume 11
Issue 5
Start page 471
End page 478
Total pages 8
Editor J. Licinio
Place of publication UK
Publisher Nature Publishing Group
Collection year 2006
Language eng
Subject 321204 Mental Health
730211 Mental health
Abstract The discovery of genetic factors that contribute to schizophrenia susceptibility is a key challenge in understanding the etiology of this disease. Here, we report the identification of a novel schizophrenia candidate gene on chromosome 1q32, plexin A2 (PLXNA2), in a genome-wide association study using 320 patients with schizophrenia of European descent and 325 matched controls. Over 25 000 single-nucleotide polymorphisms (SNPs) located within approximately 14 000 genes were tested. Out of 62 markers found to be associated with disease status, the most consistent finding was observed for a candidate locus on chromosome 1q32. The marker SNP rs752016 showed suggestive association with schizophrenia (odds ratio (OR) = 1.49, P = 0.006). This result was confirmed in an independent case control sample of European Americans (combined OR = 1.38, P = 0.035) and similar genetic effects were observed in smaller subsets of Latin Americans (OR = 1.26) and Asian Americans (OR = 1.37). Supporting evidence was also obtained from two family-based collections, one of which reached statistical significance (OR = 2.2, P = 0.02). High-density SNP mapping showed that the region of association spans approximately 60 kb of the PLXNA2 gene. Eight out of 14 SNPs genotyped showed statistically significant differences between cases and controls. These results are in accordance with previous genetic findings that identified chromosome 1q32 as a candidate region for schizophrenia. PLXNA2 is a member of the transmembrane semaphorin receptor family that is involved in axonal guidance during development and may modulate neuronal plasticity and regeneration. The PLXNA2 ligand semaphorin 3A has been shown to be upregulated in the cerebellum of individuals with schizophrenia. These observations, together with the genetic results, make PLXNA2 a likely candidate for the 1q32 schizophrenia susceptibility locus.
Keyword Biochemistry & Molecular Biology
Single-nucleotide Polymorphism
Genome-wide Association
Chromosome 1q32
Schizoaffective Disorder
Cancer Susceptibility
Chromosome 1q
Genome Scan
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 76 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 15 Aug 2007, 10:46:35 EST