Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Am J Hum Genet. 2004 Oct;75(4):624-38. Epub 2004 Aug 24.

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

Author information

  • 1Center for Psychiatric Genetics, Department of Psychiatry and Behavioral Sciences, Evanston Northwestern Healthcare and Feinberg School of Medicine, Northwestern University, Evanston, IL, USA.

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.

PMID:
15329799
[PubMed - indexed for MEDLINE]
PMCID:
PMC1182049
Free PMC Article

Images from this publication.See all images (4)Free text

Figure  A1
Figure  1
Figure  2
Figure  3
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk