Can RGS4 Polymorphisms Be Viewed as Credible Risk Factors for Schizophrenia? A Critical Review of the Evidence
Open Access
- 9 February 2006
- journal article
- review article
- Published by Oxford University Press (OUP) in Schizophrenia Bulletin
- Vol. 32 (2), 203-208
- https://doi.org/10.1093/schbul/sbj058
Abstract
There has been a recent explosion in the list of putative susceptibility genes for schizophrenia (SZ). These genes have been identified on the basis of presumed pathogenesis, linkage, and genetic association studies. While several promising candidates have arisen, identification of a conclusive genetic risk factor has remained elusive. The proof would be most compelling if it stemmed from all three of these domains. In this review, we consider such evidence in relation to the regulator of G-protein signaling 4 (RGS4), a gene localized to chromosome 1q23. Disorder-specific changes in RGS4 mRNA levels have been observed in post-mortem brain samples; linkage has been reported at chromosome 1q23; and several association studies have concluded that significant associations exist. The latter are supported by a recently conducted meta-analysis. Thus, there is suggestive evidence in each of these domains implicating a role for RGS4 in SZ susceptibility. However, analogous to other promising susceptibility candidates, the nature of the genetic association, the precise polymorphism(s) conferring risk, and the functional implications of sequence variation at this gene are unclear. We review the published data and place them in the context of suggested criteria for establishing a candidate gene as a credible susceptibility factor for disorders with non-Mendelian patterns of inheritance.Keywords
This publication has 27 references indexed in Scilit:
- Bipolar I Disorder and Schizophrenia: A 440–Single-Nucleotide Polymorphism Screen of 64 Candidate Genes among Ashkenazi Jewish Case-Parent TriosAmerican Journal of Human Genetics, 2005
- Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: SchizophreniaAmerican Journal of Human Genetics, 2003
- Association and linkage analyses of RGS4 polymorphisms in schizophreniaHuman Molecular Genetics, 2002
- No Major Schizophrenia Locus Detected on Chromosome 1q in a Large Multicenter SampleScience, 2002
- Chromosome 1 loci in Finnish schizophrenia familiesHuman Molecular Genetics, 2001
- Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophreniaMolecular Psychiatry, 2001
- Genomewide Genetic Linkage Analysis Confirms the Presence of Susceptibility Loci for Schizophrenia, on Chromosomes 1q32.2, 5q33.2, and 8p21-22 and Provides Support for Linkage to Schizophrenia, on Chromosomes 11q23.3-24 and 20q12.1-11.23American Journal of Human Genetics, 2001
- Genome-wide scan for schizophrenia in the Finnish population: evidence for a locus on chromosome 7q22Human Molecular Genetics, 2000
- The Regulator of G Protein Signaling FamilyAnnual Review of Pharmacology and Toxicology, 2000
- A Genomewide Screen for Schizophrenia Genes in an Isolated Finnish Subpopulation, Suggesting Multiple Susceptibility LociAmerican Journal of Human Genetics, 1999