Abstract
Background
The gene encoding the regulator of G-protein signaling 4 has recently been associated
with susceptibility to schizophrenia. This finding is particularly interesting, because
it was replicated within the same study and also because there are functional, positional,
and expression data to support the regulator of G-protein signaling 4 as a schizophrenia
candidate gene. Although the original report was highly suggestive, a limitation was
that the study was conducted on rather small samples.
Methods
We have examined a large case (n = 709) control (n = 710) sample for association between schizophrenia using four markers investigated
in the earlier study, denoted single nucleotide polymorphisms 1, 4, 7, and 18.
Results
We were able to replicate the associations with single nucleotide polymorphisms 4
and 18 that had previously been reported individually and have also identified significant
association with haplotypes constructed from single nucleotide polymorphisms 1 and
4.
Conclusions
Our data give modest support for the hypothesis that the regulator of G-protein signaling
4 is a susceptibility gene for schizophrenia.
Keywords
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References
- A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain.Am J Hum Genet. 2003; 73: 152-161
- Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22.Science. 2000; 288: 678-682
- Fluorescence polarization in homogenous nucleic acid analysis.Genome Res. 1999; 9: 492-498
- Association and linkage analyses of RGS4 polymorphisms in schizophrenia.Hum Mol Genet. 2002; 11: 1373-1380
- Inhibition of G protein-mediated MAP kinase activation by a new mammalian gene family.Nature. 1996; 379: 742-746
- Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia.Proc Natl Acad Sci U S A. 2001; 98: 4746-4751
- Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.Nature. 2001; 411: 599-603
- Replication validity of genetic association studies.Nat Genet. 2001; 29: 306-309
- Analysis of complex brain disorders with gene expression microarrays.Trends Neurosci. 2001; 24: 479-486
- Disease-specific changes in regulator of G-protein signalling 4 (RGS4) expression in schizophrenia.Mol Psychiatry. 2001; 6: 293-301
- Candidate gene association studies of schizophrenia.Am J Hum Genet. 1999; 65: 587-592
- Association studies in psychiatric genetics.Mol Psychiatry. 1997; 2: 270-273
- Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families.Am J Hum Genet. 2003; 72: 185-190
- Association of neuregulin 1 with schizophrenia confirmed in a Scottish population.Am J Hum Genet. 2003; 72: 83-87
- Neuregulin 1 and susceptibility to schizophrenia.Am J Hum Genet. 2002; 71: 877-892
- Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia.Am J Hum Genet. 2002; 71: 337-348
- Striatal gene expression of RGS2 and RGS4 is specifically mediated by dopamine D1 and D2 receptors.J Neurochem. 2003; 84: 1118-1127
- The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases. II. Individual genotyping.Genome Res. 1999; 9: 234-241
- Identification of novel ErbB3-interacting factors using the split-ubiquitin membrane yeast two-hybrid system.Genome Res. 2003; 13: 1744-1753
- Oligodendrocyte dysfunction in schizophrenia and bipolar disorder.Lancet. 2003; 362: 798-805
University of Pittsburgh (2003): Information concerning the RGS4 gene. Available at: http://www.pitt.edu/AFShome/n/i/nimga/public/html/ research/RGS4/Accessed on November 2, 2003.
- A two-stage genome scan for schizophrenia susceptibility genes in 196 affected sibling pairs.Hum Mol Genet. 1999; 8: 1729-1739
Williams, N.M., Preece, A., Morris, D.W., Spurlock, G., Bray, N.J., Stephens, M., et al (2003): Confirmation in two independent samples that dystobrevin binding protein (DTNBP1) is a susceptibility locus for schizophrenia. Arch Gen Psychiatry.
- Support for genetic variation in neuregulin 1 and susceptibility to schizophrenia.Mol Psychiatry. 2003; 8: 485-487
- SCAN.Arch Gen Psychiatry. 1990; 47: 589-593
- The Measurement and Classification of Psychiatric Illness.Cambridge University Press, Cambridge, MA1974
- Model-free analysis and permutation test for allelic associations.Hum Hered. 2000; 50: 133-139
Article info
Publication history
Accepted:
November 5,
2003
Received in revised form:
November 3,
2003
Received:
July 30,
2003
Identification
Copyright
© 2004 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
