Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia

Duan, JB, Martinez, M, Sanders, AR, Hou, CP, Saitou, N, Kitano, T, Mowry, BJ, Crowe, RR, Silverman, JM, Levinson, DF and Gejman, PV (2004) Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia. American Journal of Human Genetics, 75 4: 624-638. doi:10.1086/424887


Author Duan, JB
Martinez, M
Sanders, AR
Hou, CP
Saitou, N
Kitano, T
Mowry, BJ
Crowe, RR
Silverman, JM
Levinson, DF
Gejman, PV
Title Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
Publication date 2004
Sub-type Article (original research)
DOI 10.1086/424887
Volume 75
Issue 4
Start page 624
End page 638
Total pages 15
Editor S. T. Warren
Place of publication USA
Publisher University of Chicago Press
Collection year 2004
Language eng
Subject C1
321021 Psychiatry
730211 Mental health
Abstract Several linkage studies across multiple population groups provide convergent support for a susceptibility locus for schizophrenia - and, more recently, for bipolar disorder - on chromosome 6q13-q26. We genotyped 192 European-ancestry and African American (AA) pedigrees with schizophrenia from samples that previously showed linkage evidence to 6q13-q26, focusing on the MOXD1-STX7-TRARs gene cluster at 6q23.2, which contains a number of prime candidate genes for schizophrenia. Thirty-one screening single-nucleotide polymorphisms (SNPs) were selected, providing a minimum coverage of at least 1 SNP/20 kb. The association observed with rs4305745 (P = .0014) within the TRAR4 (trace amine receptor 4) gene remained significant after correction for multiple testing. Evidence for association was proportionally stronger in the smaller AA sample. We performed database searches and sequenced genomic DNA in a 30-proband subsample to obtain a high-density map of 23 SNPs spanning 21.6 kb of this gene. Single-SNP analyses and also haplotype analyses revealed that rs4305745 and/or two other polymorphisms in perfect linkage disequilibrium (LD) with rs4305745 appear to be the most likely variants underlying the association of the TRAR4 region with schizophrenia. Comparative genomic analyses further revealed that rs4305745 and/or the associated polymorphisms in complete LD with rs4305745 could potentially affect gene expression. Moreover, RT-PCR studies of various human tissues, including brain, confirm that TRAR4 is preferentially expressed in those brain regions that have been implicated in the pathophysiology of schizophrenia. These data provide strong preliminary evidence that TRAR4 is a candidate gene for schizophrenia; replication is currently being attempted in additional clinical samples.
Keyword Genetics & Heredity
Single-nucleotide Polymorphisms
Bipolar-affective-disorder
Amino-acid Oxidase
Genome Scan
Linkage Analysis
Fluorescence-polarization
Trace Amines
6p22.3 Gene
Locus
Dopamine
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2005 Higher Education Research Data Collection
School of Medicine Publications
 
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