Linkage disequilibrium patterns and functional analysis of RGS4 polymorphisms in relation to schizophrenia

Kodavali V. Chowdari, Mikhil Bamne, Joel Wood, Michael E. Talkowski, Karoly Mirnics, Pat Levitt, David A. Lewis, Vishwajit L. Nimgaonkar

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)118-126
Number of pages9
JournalSchizophrenia bulletin
Volume34
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Association
  • Linkage disequilibrium
  • Promoter
  • RGS4
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health

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    Chowdari, K. V., Bamne, M., Wood, J., Talkowski, M. E., Mirnics, K., Levitt, P., Lewis, D. A., & Nimgaonkar, V. L. (2008). Linkage disequilibrium patterns and functional analysis of RGS4 polymorphisms in relation to schizophrenia. Schizophrenia bulletin, 34(1), 118-126. https://doi.org/10.1093/schbul/sbm042