Association and linkage analyses of RGS4 polymorphisms in schizophrenia
Abstract
Gene expression analyses of postmortem cerebral cortex suggest that transcription of the regulator of G-protein signaling 4 (RGS4) is decreased in a diagnosis-specific manner in subjects with schizophrenia. To evaluate the possible role of RGS4 in the pathogenesis of schizophrenia, we conducted genetic association and linkage studies using samples ascertained independently in Pittsburgh and New Delhi and by the NIMH Collaborative Genetics Initiative. Using the transmission disequilibrium test, significant transmission distortion was observed in the Pittsburgh and NIMH samples. Among single-nucleotide polymorphisms (SNPs) spanning approximately 300 kb, significant associations involved four SNPs localized to a 10 kb region at RGS4, but the associated haplotypes differed. A trend for transmission distortion was also present in the Indian sample for haplotypes incorporating the same SNPs. Consistent with the linkage/association observed from the family-based tests, samples with affected siblings (NIMH, India) showed higher levels of allele sharing, identical by descent, at RGS4. When the US patients were contrasted to two population-based control samples, however, no significant differences were observed. To check the specificity of the transmission bias, we therefore examined US families with bipolar I disorder (BD1) probands. This sample also showed a trend for transmission distortion, and differed significantly from the population-based controls for the four-SNP haplotypes te…
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RGS4 levels are greatly reduced in the PFC of patients with schizophrenia, and there is evidence of genetic alterations in RGS4 in some families with schizophrenia or bipolar disorder.
“RGS4 levels are greatly reduced in the PFC of patients with schizophrenia134,135, and there is evidence of genetic alterations in RGS4 in some families with schizophrenia or bipolar disorder136,137.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [136]
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- Authors
- Chowdari, K. V.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Chowdari, K. V.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-06-01
- Volume
- 11
- Issue
- 12
- Pages
- 1373-1380
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2133957865
- Cited by
- 368
- References
- 5
- Citations by year
- 2024: 1 · 2023: 6 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 7 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 2 · 2013: 13 · 2012: 16
- FWCI
- 20.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1k02mh001489-01a1, 5r29mh053459-05)
- National Institute of Mental Health (MH 57881, MH01489, MH56242, MH 45156, MH 53459, P50MH045156, MH30915)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- RGS4, schizophrenia, genetic association, genetic linkage, single nucleotide polymorphisms, transmission disequilibrium test, haplotypes, bipolar I disorder, gene expression profiling, cerebral cortex, susceptibility genes, identical by descent, affected siblings
- MeSH terms
- Bipolar Disorder, Cerebral Cortex, Chromosome Mapping, Haplotypes, Humans, Molecular Sequence Data, Schizophrenia, Linkage Disequilibrium, Sequence Analysis, DNA, Polymorphism, Single Nucleotide, RGS Proteins, Gene Expression Profiling
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