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Molecular analysis of schizophrenia by the integrated approach

Research Project

Project/Area Number 14207103
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Human genetics
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

FUKUMAKI Yasuyuki  Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (90128083)

Co-Investigator(Kenkyū-buntansha) IWAKI Akiko  Kyushu University, Medical Institute of Bioregulation, Researce Associate, 生体防御医学研究所, 助手 (30253454)
Project Period (FY) 2002 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥53,040,000 (Direct Cost: ¥40,800,000、Indirect Cost: ¥12,240,000)
Fiscal Year 2005: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2004: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Fiscal Year 2003: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Fiscal Year 2002: ¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000)
Keywordsschizophrenia / affected sib-pair analysis / association study / glutamate receptor / polymorphism / linkage disequilibrium / phencyclidine / knockout mouse / 覚醒剤 / 精神分裂病(統合失調症)
Research Abstract

1.Linkage studies : The first genome-wide scan using 417 STR markers in 130 families with affected sib-pairs revealed that ten chromosomes (1,2,3,4,5,8,9,14,17, and 20) had at least one region with a nominal p value <0.05. The second genome-wide scan using 5,861 SNPs in 236 Japanese families including 122 ones used in the first scan revealed that significant evidence of linkage of schizophrenia to 1p21.1-1p13.1 and suggestive evidence of linkage to 14q11.2, 4q11.2-q13.2 and 20p12.1-p11.2.
2.Association studies : Based on the glutamatergic dysfunction hypothesis for the pathogenesis of schizophrenia, we conducted. a systematic study of associations between glutamate receptor genes and schizophrenia. We selected SNPs evenly distributed across the relevant gene regions for single marker and haplotype association studies. We found significant associations of haplotypes of GRIN2D, GRIA4, GRM3 and GRM8 with schizophrenia. Genome-wide association study using 27,000 STR markers is on the way. The second set of screening showed significant associations of 720 markers with schizophrenia. The third and fourth sets of screening followed by dense SNP typing will elucidate the susceptibility loci for schizophrenia.
3.Model animal-based studies :
(i)PCP is known to cause schizophrenia-like symptoms in human and animals, providing a well-suited model for schizophrenia. We screened the PCP-responsible genes by the microarray-based procedure using brain samples of PCP- administrated rats. We selected 10 genes differentially expressed at the level of more than 2.5 folds due to the PCP treatment. We are now doing association study of these genes with schizophrenia.
(ii) To evaluate the involvement of GRIA4 in pathogenesis of schizophrenia, we generated GluR4 deficient mice by the homologous recombination technique. Heterozygous and homozygous mutant mice were born alive, appeared normal, and were fertile in adult. For behavioral examination, a 129/sv x C57BI/6J backcross is under way.

Report

(5 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (47 results)

All 2006 2005 2004 2003 2002 Other

All Journal Article (32 results) Book (2 results) Patent(Industrial Property Rights) (1 results) Publications (12 results)

  • [Journal Article] Association study of polymorphisms in the GluR7, KA1 and KA2 kainate receptor genes (GRIK3, GRIK4, GRIK5) with schizophrenia.2006

    • Author(s)
      Shibata, H. et al.
    • Journal Title

      Psychiatry Res. 141(1)

      Pages: 39-51

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Association study of polymorphisms in the GluR7, KA1 and KA2 kainate receptor genes (GRIK3,GRIK4,GRIK5 ) with schizophrenia.2006

    • Author(s)
      Shibata, H. et al.
    • Journal Title

      Psychiatry Res. 141(1)

      Pages: 39-51

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Association study of polymorphisms in the GluR7,KA1 and KA2 kainate receptor genes (GRIK3,GRIK4,GRIK5) with schizophrenia.2006

    • Author(s)
      Shibata, H. et al.
    • Journal Title

      Psychiatry Res. 141(1)

      Pages: 39-51

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identification of single-nucleotide polymorphisms in the human N-nethyl-D-aspartate receptor subunit NR2D gene, GRIN2D, and association study with schizophrenia.2005

    • Author(s)
      Makino, C. et al.
    • Journal Title

      Psychiatr. Genet. 15(3)

      Pages: 215-224

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2,with schizophrenia.2005

    • Author(s)
      Lee, H.J.et al.
    • Journal Title

      Behav. Brain Funct. 1

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility Loci on chromosomes 1p, 14q, and 20p.2005

    • Author(s)
      JSSLG
    • Journal Title

      Am. J. Genet. 77(6)

      Pages: 937-944

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of single-nucleotide polymorphisms in the human N-methyl-D-aspartate receptor subunit NR2D gene, GRIN2D, and association study with schizophrenia.2005

    • Author(s)
      Makino, C. et al.
    • Journal Title

      Psychiatr.Genet. 15(3)

      Pages: 215-221

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia.2005

    • Author(s)
      Lee, H.et al.
    • Journal Title

      Behav.Brain Funct. 1

      Pages: 15-15

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14% and 20p.2005

    • Author(s)
      JSSLG
    • Journal Title

      Am.J.Hum.Genet. 77(6)

      Pages: 937-944

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia.2005

    • Author(s)
      Lee, HJ. et al.
    • Journal Title

      Behav.Brain Funct. 1

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility Loci on chromosomes 1p,14q, and 20p.2005

    • Author(s)
      Arinami T. et al.
    • Journal Title

      Am.J.Hum.Genet. 77(6)

      Pages: 937-944

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identification of single-nucleotide polymorphisms in the human N-methyl-D-aspartate receptor subunit NR2D gene, GRIN2D, and association study with schizophrenia.2005

    • Author(s)
      Makino, C.
    • Journal Title

      Psychiatric Genetics 印刷中

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia.2004

    • Author(s)
      Takaki, H. et al.
    • Journal Title

      Am. J. Genet. 128B(1)

      Pages: 6-14

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Association study of polymorphisms in the excitatory amino acid transporter 2 gene (SLC1A2) with schizophrenia.2004

    • Author(s)
      Deng, X. et al.
    • Journal Title

      BMC Psychiatry 4

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia.2004

    • Author(s)
      Takaki, H. et al.
    • Journal Title

      Am.J.Med.Genet. 128(1)

      Pages: 6-14

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene(GRM8) with schizophrenia.2004

    • Author(s)
      Takaki, H.
    • Journal Title

      American Journal of Medical Genetics 128B・1

      Pages: 6-14

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Association study of polymorphisms in the excitatory amino acid transporter 2 gene(SLC1A2) with schizophrenia.2004

    • Author(s)
      Deng, X.
    • Journal Title

      BMC Psychiatry 4・1

      Pages: 21-21

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Distal Sox binding elements of the αB-crystallin gene show lens enhancer activity in transgenic mouse embryos.2004

    • Author(s)
      Ijichi, N.
    • Journal Title

      Journal of Biochemistry 135・3

      Pages: 413-420

    • Related Report
      2004 Annual Research Report
  • [Journal Article] TGFB1 mutations in four new families with Camurati-Engelmann disease : confirmation of independently arising LAP-domain-specific mutations.2004

    • Author(s)
      Kinoshita, A.
    • Journal Title

      American Journal of Medical Genetics 127A・1

      Pages: 104-107

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Selective changes in the shapes of parasagittal bands of Aldoc(Zebrin) mRNA in the rat vermis of the cerebellum after repeated methamphetamine injection.2004

    • Author(s)
      Hamamura, M.
    • Journal Title

      Cerebellum 3・4

      Pages: 236-247

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Positive association of the AMPA receptor subunit G1uR4 (GRIA4) haplotype with schizophrenia : linkage disequilibrium mapping using SNPs evenly distributed across the gene region.2003

    • Author(s)
      Makino, C. et al.
    • Journal Title

      Am. J. Med. Genet. 116B(1)

      Pages: 17-22

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (GRM3) with schizophren.2003

    • Author(s)
      Fujii, Y. et al.
    • Journal Title

      Psychiatr.Genet. 13(2)

      Pages: 71-78

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Glutamate receptor genes as candidates for schizophrenia susceptibility.2003

    • Author(s)
      Fukumaki, Y., Shibata, H.
    • Journal Title

      Drug Develop. Res. 60

      Pages: 137-151

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Initial genome-wide scan for linkage with schizophrenia in Japanese Schizophrenia Sib-pair Linkage Group (JSSLG) families.2003

    • Author(s)
      JSSLG
    • Journal Title

      Am. J. Med. Genet. 120B(1)

      Pages: 22-28

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Positive association of the AMPA receptor subunit GluR4 (GRIA4) haplotype with schizophrenia : linkage disequilibrium mapping using SNPs evenly distributed across the gene region.2003

    • Author(s)
      Makino, C. et al.
    • Journal Title

      Am.J.Med.Genet. 116B(1)

      Pages: 17-22

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (GRM3) with schizophrenia.2003

    • Author(s)
      Fujii, Y. et al.
    • Journal Title

      Psychiatr.Genet. 13(2)

      Pages: 71-78

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Glutamate receptor genes as candidates for schizophrenia susceptibility.2003

    • Author(s)
      Fukumaki, Y., Shibata, H.
    • Journal Title

      Drug Develop.Res. 60

      Pages: 137-151

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Initial genome-wide scan for linkage with schizophrenia in Japanese Schizophrenia Sib-pair Linkage Group (JSSLG) families.2003

    • Author(s)
      JSSLG
    • Journal Title

      Am.J.Med.Genet. 120B(1)

      Pages: 22-28

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Polymorphism analysis of the upstream of the human N-methy1-D-aspartate receptor subunit NR1 gene (GRIN1) : implications for schizophrenia.2002

    • Author(s)
      Tani, A. et al.
    • Journal Title

      Schizophr.Res. 58(1)

      Pages: 83-86

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Association study of polymorphisms in the G1uR6 kainate receptor gene (GRIK2) with schizophrenia.2002

    • Author(s)
      Shibata, H. et al.
    • Journal Title

      Psychiatry Res. 113(1-2)

      Pages: 59-67

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Polymorphism analysis of the upstream region of the human N-methyl-D-aspartate receptor subunit NR1 gene (GRIN1) : implications for schizophrenia.2002

    • Author(s)
      Tani, A. et al.
    • Journal Title

      Schizophr.Res. 58(1)

      Pages: 83-86

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Association study of polymorphisms in the GluR6 kainate receptor gene (GRIK2 ) with schizophrenia.2002

    • Author(s)
      Shibata, H. et al.
    • Journal Title

      Psychiatry Res. 113(1-2)

      Pages: 59-67

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 血液の事典2004

    • Author(s)
      服巻 保幸 共著(平井, 押味, 坂田編)
    • Total Pages
      397
    • Publisher
      朝倉書店
    • Related Report
      2004 Annual Research Report
  • [Book] 図説 分子病態学 3版 遺伝子病の概念と分子構造(一瀬白帝, 鈴木宏治 編著)2003

    • Author(s)
      服巻 保幸
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 統合失調症関連代謝型グルタミン酸受容体遺伝内一塩基多型およびその同定方法2002

    • Inventor(s)
      服巻 保幸, 柴田 弘紀, 築原 智之
    • Industrial Property Rights Holder
      服巻 保幸, 柴田 弘紀, 築原 智之
    • Industrial Property Number
      2002-337434
    • Filing Date
      2002-11-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Takaki, H.: "Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia"American Journal of Medical Genetics. (印刷中).

    • Related Report
      2003 Annual Research Report
  • [Publications] Makino, C.: "Positive association of the AMPA receptor subunit GluR4(GRIA4) haplotype with schizophrenia : linkage disequilibrium mapping using SNPs evenly distributed across the gene region"American Journal of Medical Genetics. 116B・1. 17-22 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arinami, T.: "Initial genome-wide scan for linkage with schizophrenia in Japanese Schizopherenia Sib-pair Linkage Group (JSSLG) families"American Journal of Medical Genetics. 120B・1. 22-28 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujii, Y.: "Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (GRM3) with schizophrenia"Psychiatric Genetics. 13・2. 71-76 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukumaki, Y.: "Glutamate receptor genes as candidates for schizophrenia susceptibility"Drug Development Research. 60・2. 137-151 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 服巻 保幸: "精神疾患のゲノム解析-統合失調症を例にして"Molecular Medicine. 40・1. 84-91 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 服巻 保幸(共著): "図説 分子病態学"中外医学社. 501 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tani, A. et al.: "Polymorphism analysis of the upstream region of the human N-methyl-D-aspartate receptor subunit NR1 gene(GRIN1) : implications for schizophrenia"Schizophrenia Research. 58. 83-86 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shibata, H. et al.: "Association study of polymorphisms in the GluR6 kainate receptor gene(GRIK2) with schizophrenia"Psychiatry Research. 113. 59-67 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Makino, C. et al.: "Positive association of the AMPA receptor subunit GluR4 gene(GRIA4) haplotype with schizophrenia : linkage disequilibrium mapping using SNPs evenly distributed across the gene region"American Journal of Medical Genetics. 116B. 17-22 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujii, Y. et al.: "Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene(GRM3) with schizophrenia"Psychiatry Genetics. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arinami, T. et al.: "Initial genome-wide sxan for linkage with schizophrenia in the Japanese Schizophrenia Sib-pair Linage Group(JSSLG) families"American Journal of Medical Genetics. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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