Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia
Article first published online: 20 JUL 2009
Copyright © 2004 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 128B, Issue 1, pages 6–14, 1 July 2004
How to Cite
Takaki, H., Kikuta, R., Shibata, H., Ninomiya, H., Tashiro, N. and Fukumaki, Y. (2004), Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia. Am. J. Med. Genet., 128B: 6–14. doi: 10.1002/ajmg.b.20108
- Issue published online: 20 JUL 2009
- Article first published online: 20 JUL 2009
- Manuscript Accepted: 26 JUN 2003
- Manuscript Received: 7 APR 2003
- Grant-in-Aid for Scientific Research on Priority Areas “Medical Genome Science”
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- haplotype analysis;
- linkage disequilibrium (LD)
The glutamatergic dysfunction has been implicated in pathophysiology of schizophrenia. The Group III metabotropic glutamate receptor 4 (mGluR4), 6, 7, and 8 are thought to modulate glutamatergic transmission in the brain by inhibiting glutamate release at the synapse. We tested association of schizophrenia with GRM8 using 22 single nucleofide polymorphisms (SNPs) with the average intervals of 40.3 kb in the GRM8 region in 100 case-control pairs for the SNPs. Although we observed significant associations of schizophrenia with two SNPs, SNP18 (rs2237748, allele: P = 0.0279; genotype: P = 0.0124) and SNP19 (rs2299472, allele: P = 0.0302; genotype: P = 0.0127), none of two SNPs showed significant association with disease after Bonferroni correction. Both SNP18 and SNP19 were included in a large region (>330 kb) in which SNPs are in linkage disequilibrium (LD) at the 3′ region of GRM8. We also tested haplotype association of schizophrenia with constructed haplotypes of the SNPs in LD. Significant associations were detected for the combinations of SNP5-SNP6 (χ2 = 18.12, df = 3, P = 0.0004, P corr = 0.0924 with Bonferroni correction), SNP4-SNP5-SNP6 (χ2 = 27.50, df = 7, P = 0.0075, P corr = 0.015 with Bonferroni correction), and SNP5-SNP6-SNP7 (χ2 = 23.92, df = 7, P = 0.0011, P corr = 0.0022 with Bonferroni correction). Thus, we conclude that at least one susceptibility locus for schizophrenia is located within the GRM8 region in Japanese. © 2004 Wiley-Liss, Inc.