Skip Navigation



Schizophrenia Bulletin Advance Access published online on May 21, 2007
Schizophrenia Bulletin, doi:10.1093/schbul/sbm042
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
34/1/118    most recent
sbm042v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Chowdari, K. V.
Right arrow Articles by Nimgaonkar, V. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chowdari, K. V.
Right arrow Articles by Nimgaonkar, V. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Linkage Disequilibrium Patterns and Functional Analysis of RGS4 Polymorphisms in Relation to Schizophrenia

Kodavali V. Chowdari2, Mikhil Bamne2, Wood Joel2, Michael E. Talkowski3, Karoly Mirnics4, Pat Levitt5, David A. Lewis2 and Vishwajit L. Nimgaonkar1,3
2 Department of Psychiatry, WPIC, University of Pittsburgh, Pittsburgh, PA 15213, USA
3 Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA
4 Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA
5 Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA

1 To whom correspondence should be addressed; Departments of Psychiatry and Human Genetics University of Pittsburgh School of Medicine and Public Health Western Psychiatric Institute and Clinic, Room 441 3811 O'Hara St. Pittsburgh, PA 15213; tel: 412-246-6353, fax: 412-246-6350, e-mail: nimga{at}pitt.edu.

The regulator of G-protein signaling 4 (RGS4, chromosome 1q23.3) plays a critical role in G-protein function. Four common single-nucleotide polymorphisms (SNPs) localized between the 5' upstream sequence and the first intron, as well as 2 haplotypes derived from these SNPs may confer liability to schizophrenia (SZ). However, the pattern of associations varies among samples. To help clarify the putative associations, we report the following analyses: (1) a comprehensive catalog of common polymorphisms, (2) linkage disequilibrium (LD) and association analyses using these SNPs, and (3) functional analysis based on dual-luciferase promoter assays. We identified 62 SNPs from a 20-kb genomic region spanning RGS4, of which 26 are common polymorphisms with a minor allele frequency (MAF) of >5%. LD analysis suggested 5 clusters of SNPs (r2 > .8). Association analyses using the novel SNPs were consistent with the prior reports, but further localization was constrained by significant LD across the region. The 2 haplotypes reported to confer liability to SZ had significant promoter activity compared with promoterless constructs, suggesting a functional role for both haplotypes. Further analyses of promoter sequences are warranted to understand transcriptional regulation at RGS4. This information will be useful for further analysis of samples in which genetic association of RGS4 polymorphisms with SZ has been reported.

Keywords: RGS4 / association / linkage disequilibrium / promoter / schizophrenia


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.