Association study of polymorphisms in the group III metabotropic glutamate receptor genes, GRM4 and GRM7, with schizophrenia
Based on the hypothesis that a glutamatergic dysfunction is involved in the pathophysiology of schizophrenia, we have been conducting systematic studies on the association between glutamate receptor genes and schizophrenia. Here we report association studies of schizophrenia with polymorphisms in gr...
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| Published in | Psychiatry research Vol. 167; no. 1; pp. 88 - 96 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Kidlington
Elsevier Ireland Ltd
15.05.2009
Elsevier |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0165-1781 1872-7123 |
| DOI | 10.1016/j.psychres.2007.12.002 |
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| Abstract | Based on the hypothesis that a glutamatergic dysfunction is involved in the pathophysiology of schizophrenia, we have been conducting systematic studies on the association between glutamate receptor genes and schizophrenia. Here we report association studies of schizophrenia with polymorphisms in group III metabotropic glutamate receptor genes,
GRM4 and
GRM7. We selected 8 and 43 common SNPs distributed in the entire gene regions of
GRM4 (>
111 kb) and
GRM7 (>
900 kb), respectively. We scanned significant associations with schizophrenia using 100 case-control pairs of Japanese. We identified two neighboring SNPs (rs12491620 and rs1450099) in
GRM7 showing highly significant haplotype association with schizophrenia surviving the FDR correction. We then performed additional typing of the two SNPs using the expanded sample set (404 cases and 420 controls) and confirmed the significant association with the disease. We conclude that at least one susceptibility locus for schizophrenia is located within or nearby
GRM7, whereas
GRM4 is unlikely to be a major susceptibility gene for schizophrenia in the Japanese population. |
|---|---|
| AbstractList | Based on the hypothesis that a glutamatergic dysfunction is involved in the pathophysiology of schizophrenia, we have been conducting systematic studies on the association between glutamate receptor genes and schizophrenia. Here we report association studies of schizophrenia with polymorphisms in group III metabotropic glutamate receptor genes, GRM4 and GRM7. We selected 8 and 43 common SNPs distributed in the entire gene regions of GRM4 (>111 kb) and GRM7 (>900 kb), respectively. We scanned significant associations with schizophrenia using 100 case-control pairs of Japanese. We identified two neighboring SNPs (rs12491620 and rs1450099) in GRM7 showing highly significant haplotype association with schizophrenia surviving the FDR correction. We then performed additional typing of the two SNPs using the expanded sample set (404 cases and 420 controls) and confirmed the significant association with the disease. We conclude that at least one susceptibility locus for schizophrenia is located within or nearby GRM7, whereas GRM4 is unlikely to be a major susceptibility gene for schizophrenia in the Japanese population.Based on the hypothesis that a glutamatergic dysfunction is involved in the pathophysiology of schizophrenia, we have been conducting systematic studies on the association between glutamate receptor genes and schizophrenia. Here we report association studies of schizophrenia with polymorphisms in group III metabotropic glutamate receptor genes, GRM4 and GRM7. We selected 8 and 43 common SNPs distributed in the entire gene regions of GRM4 (>111 kb) and GRM7 (>900 kb), respectively. We scanned significant associations with schizophrenia using 100 case-control pairs of Japanese. We identified two neighboring SNPs (rs12491620 and rs1450099) in GRM7 showing highly significant haplotype association with schizophrenia surviving the FDR correction. We then performed additional typing of the two SNPs using the expanded sample set (404 cases and 420 controls) and confirmed the significant association with the disease. We conclude that at least one susceptibility locus for schizophrenia is located within or nearby GRM7, whereas GRM4 is unlikely to be a major susceptibility gene for schizophrenia in the Japanese population. Based on the hypothesis that a glutamatergic dysfunction is involved in the pathophysiology of schizophrenia, we have been conducting systematic studies on the association between glutamate receptor genes and schizophrenia. Here we report association studies of schizophrenia with polymorphisms in group III metabotropic glutamate receptor genes, GRM4 and GRM7. We selected 8 and 43 common SNPs distributed in the entire gene regions of GRM4 (> 111 kb) and GRM7 (> 900 kb), respectively. We scanned significant associations with schizophrenia using 100 case-control pairs of Japanese. We identified two neighboring SNPs (rs12491620 and rs1450099) in GRM7 showing highly significant haplotype association with schizophrenia surviving the FDR correction. We then performed additional typing of the two SNPs using the expanded sample set (404 cases and 420 controls) and confirmed the significant association with the disease. We conclude that at least one susceptibility locus for schizophrenia is located within or nearby GRM7, whereas GRM4 is unlikely to be a major susceptibility gene for schizophrenia in the Japanese population. Abstract Based on the hypothesis that a glutamatergic dysfunction is involved in the pathophysiology of schizophrenia, we have been conducting systematic studies on the association between glutamate receptor genes and schizophrenia. Here we report association studies of schizophrenia with polymorphisms in group III metabotropic glutamate receptor genes, GRM4 and GRM7 . We selected 8 and 43 common SNPs distributed in the entire gene regions of GRM4 (> 111 kb) and GRM7 (> 900 kb), respectively. We scanned significant associations with schizophrenia using 100 case-control pairs of Japanese. We identified two neighboring SNPs (rs12491620 and rs1450099) in GRM7 showing highly significant haplotype association with schizophrenia surviving the FDR correction. We then performed additional typing of the two SNPs using the expanded sample set (404 cases and 420 controls) and confirmed the significant association with the disease. We conclude that at least one susceptibility locus for schizophrenia is located within or nearby GRM7 , whereas GRM4 is unlikely to be a major susceptibility gene for schizophrenia in the Japanese population. Based on the hypothesis that a glutamatergic dysfunction is involved in the pathophysiology of schizophrenia, we have been conducting systematic studies on the association between glutamate receptor genes and schizophrenia. Here we report association studies of schizophrenia with polymorphisms in group III metabotropic glutamate receptor genes, GRM4 and GRM7. We selected 8 and 43 common SNPs distributed in the entire gene regions of GRM4 (>111 kb) and GRM7 (>900 kb), respectively. We scanned significant associations with schizophrenia using 100 case-control pairs of Japanese. We identified two neighboring SNPs (rs12491620 and rs1450099) in GRM7 showing highly significant haplotype association with schizophrenia surviving the FDR correction. We then performed additional typing of the two SNPs using the expanded sample set (404 cases and 420 controls) and confirmed the significant association with the disease. We conclude that at least one susceptibility locus for schizophrenia is located within or nearby GRM7, whereas GRM4 is unlikely to be a major susceptibility gene for schizophrenia in the Japanese population. |
| Author | Chikuhara, Tomoyuki Kikuta, Rumiko Sakai, Mayumi Fukumaki, Yasuyuki Iwata, Nakao Ninomiya, Hideaki Tani, Ayako Ozaki, Norio Tashiro, Nobutada Shibata, Hiroki |
| Author_xml | – sequence: 1 givenname: Hiroki surname: Shibata fullname: Shibata, Hiroki email: hshibata@gen.kyushu-u.ac.jp organization: Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan – sequence: 2 givenname: Ayako surname: Tani fullname: Tani, Ayako organization: Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan – sequence: 3 givenname: Tomoyuki surname: Chikuhara fullname: Chikuhara, Tomoyuki organization: Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan – sequence: 4 givenname: Rumiko surname: Kikuta fullname: Kikuta, Rumiko organization: Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan – sequence: 5 givenname: Mayumi surname: Sakai fullname: Sakai, Mayumi organization: Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan – sequence: 6 givenname: Hideaki surname: Ninomiya fullname: Ninomiya, Hideaki organization: Fukuoka Prefectural Dazaifu Hospital Psychiatric Center, Dazaifu, Fukuoka, Japan – sequence: 7 givenname: Nobutada surname: Tashiro fullname: Tashiro, Nobutada organization: Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan – sequence: 8 givenname: Nakao surname: Iwata fullname: Iwata, Nakao organization: Department of Psychiatry, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan – sequence: 9 givenname: Norio surname: Ozaki fullname: Ozaki, Norio organization: Department of Psychiatry, Graduate School of Medicine, Nagoya University, Nagoya, Japan – sequence: 10 givenname: Yasuyuki surname: Fukumaki fullname: Fukumaki, Yasuyuki organization: Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan |
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| Keywords | Schizophrenia Glutamate receptor Single nucleotide polymorphism Haplotype Linkage disequilibrium Psychosis Gene Social group Genetics Genetic determinism Group III mglu glutamate receptor |
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| SubjectTerms | Adult and adolescent clinical studies Biological and medical sciences Female Gene Frequency Genetic Predisposition to Disease Genome-Wide Association Study Genotype Glutamate receptor Haplotype Haplotypes - genetics Humans Linkage disequilibrium Linkage Disequilibrium - genetics Male Medical sciences Middle Aged Polymorphism, Genetic Polymorphism, Single Nucleotide - genetics Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Receptors, Glutamate - genetics Receptors, Metabotropic Glutamate - genetics Schizophrenia Schizophrenia - genetics Single nucleotide polymorphism |
| Title | Association study of polymorphisms in the group III metabotropic glutamate receptor genes, GRM4 and GRM7, with schizophrenia |
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