Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 with schizophrenia
Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. We report here association studies of schizophrenia with three glutamate transporter genes SLC1...
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| Published in | American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 144B; no. 3; pp. 271 - 278 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
05.04.2007
Wiley-Liss |
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| Online Access | Get full text |
| ISSN | 1552-4841 1552-485X |
| DOI | 10.1002/ajmg.b.30351 |
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| Abstract | Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. We report here association studies of schizophrenia with three glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 encoding the glutamate transporters EAAT3, EAAT1, and EAAT4, respectively. We initially performed the screening of the total 25 single nucleotide polymorphisms (SNPs) distributed in the three gene regions using 100 out of 400 Japanese cases and 100 out of 420 Japanese controls. After controlling the false discovery rate (FDR) at level 0.05, we observed significant associations of schizophrenia with a genotype of SNP4 (rs2097837, P = 0.007) and with haplotypes of SNP2‐SNP5 (P = 7.5 × 10−5) and SNP3‐SNP5 (P = 9.0 × 10−4) in the SLC1A6 region. The haplotype of SNP2‐SNP5 of SLC1A6 even showed marginally significant association with the disease in the full‐size sample (400 cases and 420 controls, P = 0.031). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6, whereas SLC1A1 and SLC1A3 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population. © 2006 Wiley‐Liss, Inc. |
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| AbstractList | Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. We report here association studies of schizophrenia with three glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 encoding the glutamate transporters EAAT3, EAAT1, and EAAT4, respectively. We initially performed the screening of the total 25 single nucleotide polymorphisms (SNPs) distributed in the three gene regions using 100 out of 400 Japanese cases and 100 out of 420 Japanese controls. After controlling the false discovery rate (FDR) at level 0.05, we observed significant associations of schizophrenia with a genotype of SNP4 (rs2097837, P=0.007) and with haplotypes of SNP2-SNP5 (P=7.5X10-5) and SNP3-SNP5 (P=9.0X10-4) in the SLC1A6 region. The haplotype of SNP2-SNP5 of SLC1A6 even showed marginally significant association with the disease in the full-size sample (400 cases and 420 controls, P=0.031). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6, whereas SLC1A1 and SLC1A3 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population. Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. We report here association studies of schizophrenia with three glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 encoding the glutamate transporters EAAT3, EAAT1, and EAAT4, respectively. We initially performed the screening of the total 25 single nucleotide polymorphisms (SNPs) distributed in the three gene regions using 100 out of 400 Japanese cases and 100 out of 420 Japanese controls. After controlling the false discovery rate (FDR) at level 0.05, we observed significant associations of schizophrenia with a genotype of SNP4 (rs2097837, P = 0.007) and with haplotypes of SNP2‐SNP5 (P = 7.5 × 10−5) and SNP3‐SNP5 (P = 9.0 × 10−4) in the SLC1A6 region. The haplotype of SNP2‐SNP5 of SLC1A6 even showed marginally significant association with the disease in the full‐size sample (400 cases and 420 controls, P = 0.031). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6, whereas SLC1A1 and SLC1A3 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population. © 2006 Wiley‐Liss, Inc. Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. We report here association studies of schizophrenia with three glutamate transporter genes SLC1A1 , SLC1A3 , and SLC1A6 encoding the glutamate transporters EAAT3, EAAT1, and EAAT4, respectively. We initially performed the screening of the total 25 single nucleotide polymorphisms (SNPs) distributed in the three gene regions using 100 out of 400 Japanese cases and 100 out of 420 Japanese controls. After controlling the false discovery rate (FDR) at level 0.05, we observed significant associations of schizophrenia with a genotype of SNP4 (rs2097837, P = 0.007) and with haplotypes of SNP2‐SNP5 ( P = 7.5 × 10 −5 ) and SNP3‐SNP5 ( P = 9.0 × 10 −4 ) in the SLC1A6 region . The haplotype of SNP2‐SNP5 of SLC1A6 even showed marginally significant association with the disease in the full‐size sample (400 cases and 420 controls, P = 0.031). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6 , whereas SLC1A1 and SLC1A3 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population. © 2006 Wiley‐Liss, Inc. Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. We report here association studies of schizophrenia with three glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 encoding the glutamate transporters EAAT3, EAAT1, and EAAT4, respectively. We initially performed the screening of the total 25 single nucleotide polymorphisms (SNPs) distributed in the three gene regions using 100 out of 400 Japanese cases and 100 out of 420 Japanese controls. After controlling the false discovery rate (FDR) at level 0.05, we observed significant associations of schizophrenia with a genotype of SNP4 (rs2097837, P = 0.007) and with haplotypes of SNP2-SNP5 (P = 7.5 x 10(-5)) and SNP3-SNP5 (P = 9.0 x 10(-4)) in the SLC1A6 region. The haplotype of SNP2-SNP5 of SLC1A6 even showed marginally significant association with the disease in the full-size sample (400 cases and 420 controls, P = 0.031). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6, whereas SLC1A1 and SLC1A3 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population. Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. We report here association studies of schizophrenia with three glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 encoding the glutamate transporters EAAT3, EAAT1, and EAAT4, respectively. We initially performed the screening of the total 25 single nucleotide polymorphisms (SNPs) distributed in the three gene regions using 100 out of 400 Japanese cases and 100 out of 420 Japanese controls. After controlling the false discovery rate (FDR) at level 0.05, we observed significant associations of schizophrenia with a genotype of SNP4 (rs2097837, P = 0.007) and with haplotypes of SNP2-SNP5 (P = 7.5 x 10(-5)) and SNP3-SNP5 (P = 9.0 x 10(-4)) in the SLC1A6 region. The haplotype of SNP2-SNP5 of SLC1A6 even showed marginally significant association with the disease in the full-size sample (400 cases and 420 controls, P = 0.031). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6, whereas SLC1A1 and SLC1A3 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population.Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. We report here association studies of schizophrenia with three glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 encoding the glutamate transporters EAAT3, EAAT1, and EAAT4, respectively. We initially performed the screening of the total 25 single nucleotide polymorphisms (SNPs) distributed in the three gene regions using 100 out of 400 Japanese cases and 100 out of 420 Japanese controls. After controlling the false discovery rate (FDR) at level 0.05, we observed significant associations of schizophrenia with a genotype of SNP4 (rs2097837, P = 0.007) and with haplotypes of SNP2-SNP5 (P = 7.5 x 10(-5)) and SNP3-SNP5 (P = 9.0 x 10(-4)) in the SLC1A6 region. The haplotype of SNP2-SNP5 of SLC1A6 even showed marginally significant association with the disease in the full-size sample (400 cases and 420 controls, P = 0.031). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6, whereas SLC1A1 and SLC1A3 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population. |
| Author | Sakai, Mayumi Fukumaki, Yasuyuki Deng, Xiangdong Iwata, Nakao Ninomiya, Hideaki Ozaki, Norio Takeuchi, Naoko Shibata, Hiroki Rachi, Shinako |
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| Keywords | Psychosis Association Gene SNP glutamate transporter Schizophrenia Single nucleotide polymorphism Linkage equilibrium Glutamate Haplotype linkage disequilibrium |
| Language | English |
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| Notes | Naito Foundation ark:/67375/WNG-4TBNBZVN-8 ArticleID:AJMG30351 Please cite this article as follows: Deng X, Shibata H, Takeuchi N, Rachi S, Sakai M, Ninomiya H, Iwata N, Ozaki N, Fukumaki Y. 2007. Association Study of Polymorphisms in the Glutamate Transporter Genes SLC1A1, SLC1A3, and SLC1A6 With Schizophrenia. Am J Med Genet Part B 144B:271-278. Ministry of Education, Culture, Sports, Science Technology Ministry of Health, Labor and Welfare of Japan istex:192343FC8B21A36F7092FBA835BC8C4D470E7A92 Please cite this article as follows: Deng X, Shibata H, Takeuchi N, Rachi S, Sakai M, Ninomiya H, Iwata N, Ozaki N, Fukumaki Y. 2007. Association Study of Polymorphisms in the Glutamate Transporter Genes With Schizophrenia. Am J Med Genet Part B 144B:271–278. and SLC1A1 SLC1A3 , SLC1A6 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
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| PublicationTitle | American journal of medical genetics. Part B, Neuropsychiatric genetics |
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| SubjectTerms | Adult Adult and adolescent clinical studies Amino Acid Transport System X-AG - genetics Asian Continental Ancestry Group - genetics Biological and medical sciences Excitatory Amino Acid Transporter 1 - genetics Excitatory Amino Acid Transporter 3 - genetics Excitatory Amino Acid Transporter 4 - genetics Female Gene Frequency Genetic Linkage Genetic Predisposition to Disease Genotype glutamate transporter haplotype Humans linkage disequilibrium Male Medical genetics Medical sciences Middle Aged Polymorphism, Single Nucleotide Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Schizophrenia Schizophrenia - genetics SNP |
| Title | Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 with schizophrenia |
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