Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow A corrigendum has been published
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 ISI Web of Science
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 arrow Search for citing articles in:
ISI Web of Science (158)
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?

Human Molecular Genetics, 2002, Vol. 11, No. 12 1373-1380
© 2002 Oxford University Press

Association and linkage analyses of RGS4 polymorphisms in schizophrenia

Kodavali V. Chowdari1, Karoly Mirnics1,2, Prachi Semwal5, Joel Wood1, Elizabeth Lawrence3, Triptish Bhatia6, Smita N. Deshpande6,7, Thelma B.K.5,6, Robert E. Ferrell3, Frank A. Middleton2, Bernie Devlin1,3, Pat Levitt2, David A. Lewis1,4 and Vishwajit L. Nimgaonkar1,3,6,*

1Department of Psychiatry, 2Department of Neurobiology, 3Department of Human Genetics and 4Department of Neuroscience University of Pittsburgh, School of Medicine and Graduate School of Public Health; Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA, 5Department of Genetics, University of Delhi South Campus, New Delhi 110021, India, 6Indo–US Project on Schizophrenia Genetics, New Delhi 110001, India and 7Department of Psychiatry, Dr R.M.L. Hospital New Delhi 110001, India

Received January 7, 2002; Accepted March 29, 2002

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 tested in the other samples. The transmission distortion is unlikely to be due to chance, but its mechanism and specificity require further study. Our results illustrate the potential power of combining gene expression profiling and genomic analyses to identify susceptibility genes for genetically complex disorders.

* To whom correspondence should be addressed at: 3811 O'Hara St, Room 443, Pittsburgh, PA 15213, USA. Tel:+1 412 624 0823; Fax:+1 412 624 0446; Email: nimga{at}pitt.edu


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


This article has been cited by other articles:


Home page
 Schizophr BullHome page
E. Ivleva, G. Thaker, and C. A. Tamminga
Comparing Genes and Phenomenology in the Major Psychoses: Schizophrenia and Bipolar 1 Disorder
Schizophr Bull, July 1, 2008; 34(4): 734 - 742.
[Full Text] [PDF]

Home page
 Schizophr BullHome page
K. V. Chowdari, M. Bamne, J. Wood, M. E. Talkowski, K. Mirnics, P. Levitt, D. A. Lewis, and V. L. Nimgaonkar
Linkage Disequilibrium Patterns and Functional Analysis of RGS4 Polymorphisms in Relation to Schizophrenia
Schizophr Bull, January 1, 2008; 34(1): 118 - 126.
[Abstract] [Full Text] [PDF]

Home page
 Cereb CortexHome page
A. F. T. Arnsten
Catecholamine and Second Messenger Influences on Prefrontal Cortical Networks of "Representational Knowledge": A Rational Bridge between Genetics and the Symptoms of Mental Illness
Cereb Cortex, September 1, 2007; 17(suppl_1): i6 - i15.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
D. G Romero, M. Y. Zhou, L. L Yanes, M. W Plonczynski, T. R Washington, C. E Gomez-Sanchez, and E. P Gomez-Sanchez
Regulators of G-protein signaling 4 in adrenal gland: localization, regulation, and role in aldosterone secretion
J. Endocrinol., August 1, 2007; 194(2): 429 - 440.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Z. Gu, Q. Jiang, and Z. Yan
RGS4 Modulates Serotonin Signaling in Prefrontal Cortex and Links to Serotonin Dysfunction in a Rat Model of Schizophrenia
Mol. Pharmacol., April 1, 2007; 71(4): 1030 - 1039.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. W. Buckholtz, A. Meyer-Lindenberg, R. A. Honea, R. E. Straub, L. Pezawas, M. F. Egan, R. Vakkalanka, B. Kolachana, B. A. Verchinski, S. Sust, et al.
Allelic Variation in RGS4 Impacts Functional and Structural Connectivity in the Human Brain
J. Neurosci., February 14, 2007; 27(7): 1584 - 1593.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
W. Liu, E. Y. Yuen, P. B. Allen, J. Feng, P. Greengard, and Z. Yan
Adrenergic modulation of NMDA receptors in prefrontal cortex is differentially regulated by RGS proteins and spinophilin
PNAS, November 28, 2006; 103(48): 18338 - 18343.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
X. Chen, X. Wang, S. Hossain, F. A. O'Neill, D. Walsh, L. Pless, K. V. Chowdari, V. L. Nimgaonkar, S. G. Schwab, D. B. Wildenauer, et al.
Haplotypes spanning SPEC2, PDZ-GEF2 and ACSL6 genes are associated with schizophrenia
Hum. Mol. Genet., November 15, 2006; 15(22): 3329 - 3342.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Jaen and C. A. Doupnik
RGS3 and RGS4 Differentially Associate with G Protein-coupled Receptor-Kir3 Channel Signaling Complexes Revealing Two Modes of RGS Modulation: PRECOUPLING AND COLLISION COUPLING
J. Biol. Chem., November 10, 2006; 281(45): 34549 - 34560.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
B. K. Lipska, S. Mitkus, M. Caruso, T. M. Hyde, J. Chen, R. Vakkalanka, R. E. Straub, D. R. Weinberger, and J. E. Kleinman
RGS4 mRNA expression in postmortem human cortex is associated with COMT Val158Met genotype and COMT enzyme activity
Hum. Mol. Genet., September 15, 2006; 15(18): 2804 - 2812.
[Abstract] [Full Text] [PDF]

Home page
 FocusHome page
J. A. Gogos and D. J. Gerber
Schizophrenia Susceptibility Genes: Emergence of Positional Candidates and Future Directions
Focus, August 1, 2006; 4(3): 369.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
K. Iwamoto and T. Kato
Gene Expression Profiling in Schizophrenia and Related Mental Disorders
Neuroscientist, August 1, 2006; 12(4): 349 - 361.
[Abstract] [PDF]

Home page
 Schizophr BullHome page
M. E Talkowski, K. Chowdari, D. A Lewis, and V. L Nimgaonkar
Can RGS4 Polymorphisms Be Viewed as Credible Risk Factors for Schizophrenia? A Critical Review of the Evidence
Schizophr Bull, April 1, 2006; 32(2): 203 - 208.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
T. R. Peirce, N. J. Bray, N. M. Williams, N. Norton, V. Moskvina, A. Preece, V. Haroutunian, J. D. Buxbaum, M. J. Owen, and M. C. O'Donovan
Convergent Evidence for 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase as a Possible Susceptibility Gene for Schizophrenia
Arch Gen Psychiatry, January 1, 2006; 63(1): 18 - 24.
[Abstract] [Full Text] [PDF]

Home page
 Cereb CortexHome page
H. Homayoun and B. Moghaddam
Bursting of Prefrontal Cortex Neurons in Awake Rats is Regulated by Metabotropic Glutamate 5 (mGlu5) Receptors: Rate-dependent Influence and Interaction with NMDA Receptors
Cereb Cortex, January 1, 2006; 16(1): 93 - 105.
[Abstract] [Full Text] [PDF]

Home page
 J PsychopharmacolHome page
S. C. L. Gough and M. C. O'Donovan
Clustering of metabolic comorbidity in schizophrenia: a genetic contribution?
J Psychopharmacol, November 1, 2005; 19(6_suppl): 47 - 55.
[Abstract] [PDF]

Home page
 Mol. Cell. Biol.Home page
N. Grillet, A. Pattyn, C. Contet, B. L. Kieffer, C. Goridis, and J.-F. Brunet
Generation and Characterization of Rgs4 Mutant Mice
Mol. Cell. Biol., May 15, 2005; 25(10): 4221 - 4228.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
N Craddock, M C O'Donovan, and M J Owen
The genetics of schizophrenia and bipolar disorder: dissecting psychosis
J. Med. Genet., March 1, 2005; 42(3): 193 - 204.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. M. Berman, Y. Wang, Z. Liu, Q. Dong, L.-A. Burke, L. A. Liotta, R. Fisher, and X. Wu
A Functional Polymorphism in RGS6 Modulates the Risk of Bladder Cancer
Cancer Res., September 15, 2004; 64(18): 6820 - 6826.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
W. Hennah, T. Varilo, M. Kestila, T. Paunio, R. Arajarvi, J. Haukka, A. Parker, R. Martin, S. Levitzky, T. Partonen, et al.
Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects
Hum. Mol. Genet., December 1, 2003; 12(23): 3151 - 3159.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
R. Freedman
Schizophrenia
N. Engl. J. Med., October 30, 2003; 349(18): 1738 - 1749.
[Full Text] [PDF]

Home page
 Hum Mol GenetHome page
M. C. O'Donovan, N. M. Williams, and M. J. Owen
Recent advances in the genetics of schizophrenia
Hum. Mol. Genet., October 15, 2003; 12(90002): R125 - 133.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Interv.Home page
E. Costa, D. R. Grayson, and A. Guidotti
Epigenetic Downregulation of GABAergic Function in Schizophrenia: Potential for Pharmacological Intervention?
Mol. Interv., June 1, 2003; 3(4): 220 - 229.
[Abstract] [Full Text] [PDF]


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.