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Identification of susceptibility genes for psychiatric diseases on chromosome 18

Research Project

Project/Area Number 14570955
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionRIKEN (The Institute of Physical and Chemical Research)

Principal Investigator

YAMADA Kazuo  RIKEN (The Institute of Physical and Chemical Research) Brain Science Institute, Lab. for Molecular Psychiatry, Research Scientist, 分子精神科学研究チーム, 研究員 (10322695)

Co-Investigator(Kenkyū-buntansha) YOSHIKAWA Takeo  RIKEN (The Institute of Physical and Chemical Research) Brain Science Institute, Lab. for Molecular Psychiatry, Laboratory Head, 分子精神科学研究チーム, チームリーダー (30249958)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsEndogenous psychosis / Chromosome 18 / Mood disorder / Schizophrenia / Linkage disequilibrium mapping / Transmission disequilibrium test / IMPA2 gene / C18orf gene / C18orfl遺伝子 / 関連研究
Research Abstract

The pericentromeric region of chromosome 18,especially 18p11.2,is described as a schizophrenia susceptibility locus. We had previously cloned two novel brain-derived transcripts from this region : the gene for a second human myo-inosititol monophosphatase (IMPA2) and a gene of unknown function, C18orf1.
We performed a family-based LD study as the first step towards identifying relevant genetic loci around 18p11.2,and then followed up using a case-control approach. These markers covered 18p11.2 at an average density of 1/280 kb. A follow-up study of independent schizophrenics (n=214) and controls (n=313), revealed a significant association between the haplotype constructed by the D18S852 and 6409T>C and schizophrenia (P=0.00001).
In addition, we have performed a genome-wide LD survey of susceptibility loci for schizophrenia. We first typed 119 schizophrenic pedigrees (357 individuals) using 444 microsatellite markers. This analysis revealed 14 markers demonstrating significant transmissio … More n distortion. We scrutinized the most significant genomic locus on 11q11-13 by adding 26 new markers for analysis. Three-marker haplotype analysis in the region showed evidence of association with schizophrenia (most significant haplotype P=0.00005,global P=0.022). However, further support for chromosome 18 was not obtained by transmission distortion analysis.
Besides, we have genotyped 496 Japanese bipolar patients and 543 control subjects, using 17 SNPs on and around the IMPA2 gene. The distributions of haplotypes defined by -1051G>T,-708G>A,-461C>T and IVS1+1801C>T were different between control and schizophrenia groups (P=0.007). These findings suggest that the IMPA2 gene or a gene nearby may contribute to the overall genetic risk for bipolar disorder. Recently, we set out an in-vitro assay of the gene to reveal an influence of the SNPs on transcriptional activity. The present study should be expanded upon at increased marker resolution, followed by replication and confirmation tests in different sets of larger samples. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (60 results)

All Other

All Publications (60 results)

  • [Publications] Yamada K. et al.: "Family-based association study of schizophrenia with 444 markers and analysis of a new susceptibility locus mapped to 11q13.3."American Journal of Medical Genetics. 127B(1). 11-19 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toyota T. et al.: "Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B."Human Molecular Genetics. 13(5). 551-561 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arai M.et al.: "Association of neural cell adhesion molecule 1 gene polymorphisms with bipolar affective disorder in Japanese individuals."Biological Psychiatry. 55(8). 804-810 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horiuchi Y. et al.: "Possible association between a haplotype of the GABA-A receptor alpha 1 subunit gene (GABRA1) and mood disorders."Biological Psychiatry. 55(1). 40-45 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 糸川昌成ら: "臨床遣伝と病態理解-遺伝子研究からみた病態仮説"医学のあゆみ. 208(3). 146-152 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi M. et al.: "C18orf1 located on chromosome 18p11.2 may confer susceptibility to schizophrenia."Journal of Medical & Dental Sciences. 50(3). 225-229 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi M. et al.: "Two-step association analyses of the chromosome 18p11.2 region in schizophrenia detect a locus encompassing C18orf1."Molecular Psychiatry. 8(5). 467-469 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada K. et al.: "Evidence of association between gamma-aminobutyric acid type A receptor genes located on 5q34 and female patients with mood disorders."Neuroscience Letters. 349(1). 9-12 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itokawa M. et al.: "Genetic analysis of a functional GRIN2A promoter (GT)n repeat in bipolar disorder pedigrees in humans."Neuroscience Letters. 345(1). 53-56 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itokawa M. et al.: "A microsatellite repeat in the promoter of the N-methyl-D-aspartate receptor 2A subunit (GRIN2A) gene suppresses transcriptional activity and correlates with chronic outcome in schizophrenia."Pharmacogenetics. 13(5). 271-278 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toyota T. et al.: "Analysis of a cluster of polymorphisms in AKT1 gene in bipolar pedigrees : a family-based association study."Neuroscience Letters. 339(1). 5-8 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwayama-Shigeno Y. et al.: "Distribution of haplotypes derived from three common variants of the NR4A2 gene in Japanese patients with schizophrenia."American Journal of Medical Genetics. 118B(1). 20-24 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ebihara M. et al.: "Transcriptional activities of cholecystokinin promoter haplotypes and their relevance to panic disorder susceptibility."American Journal of Medical Genetics. 118B(1). 32-35 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 海老原充ら: "良性成人型家族性ミオクローヌスてんかん原因遺伝子の探索"てんかん治療研究振興財団研究年報. 15. 57-64 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohtsuki T. et al.: "Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees."Molecular Psychiatry. 7(9). 954-961 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toyota T. et al.: "Association analysis of adenylate cyclase type 9 gene using pedigree disequilibrium test in bipolar disorder."Molecular Psychiatry. 7(5). 450-452 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hattori E. et al.: "Association study of the short tandem repeat in the 5' upstream region of the cholecystokinin gene with mood disorders in the Japanese population."American Journal of Medical Genetics. 114(5). 523-526 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toyota T. et al.: "Molecular analysis, mutation screening, and association study of adenylate cyclase type 9 gene (ADCY9) in mood disorders."American Journal of Medical Genetics. 114(1). 84-92 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 山田和男ら: "精神分裂病家系を用いた染色体18番の疾患感受性座位の同定-伝達連鎖不平衡テストによる遺伝統計学的処理の比較-"脳と精神の医学. 13(3). 305-315 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 吉川武男, 糸川昌成, 山田和男: "機能性精神疾患の遺伝子研究の進歩:機能的精神疾患の系統的遺伝子解析:脳科学研究の現状と課題"じほう. 324(53-69) (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada K. et al.: "Family-based association study of schizophrenia with 444 markers and analysis of a new susceptibility locus mapped to 11q13.3."American Journal of Medical Genetics. 127B(1). 11-19 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toyota T. et al.: "Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B."Human Molecular Genetics. 13(5). 551-561 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arai M.et al.: "Association of neural cell adhesion molecule 1 gene polymorphisms with bipolar affective disorder in Japanese individuals."Biological Psychiatry. 55(8). 804-810 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horiuchi Y. et al.: "Possible association between a haplotype of the GABA-A receptor alpha 1 subunit gene (GABRA1) and mood disorders."Biological Psychiatry. 55(1). 40-45 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itokawa M. et al.: "Clinical genetics and interpretation of pathophysiology."Journal of Clinical and Experimental Medicine (IKAKU NO AYUMI). 208(3). 146-152 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi M. et al.: "C18orf1 located on chromosome 18p11.2 may confer susceptibility to schizophrenia."Journal of Medical & Dental Sciences. 50(3). 225-229 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi M. et al.: "Two-step association analyses of the chromosome 18p11.2 region in schizophrenia detect a locus encompassing C18orf1."Molecular Psychiatry. 8(5). 467-469 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada K. et al.: "Evidence of association between gamma-aminobutyric acid type A receptor genes located on 5q34 and female patients with mood disorders."Neuroscience Letters. 349(1). 9-12 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itokawa M. et al.: "Genetic analysis of a functional GRIN2A promoter (GT)n repeat in bipolar disorder pedigrees in humans."Neuroscience Letters. 345(1). 53-56 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itokawa M. et al.: "A microsatellite repeat in the promoter of the N-methyl-D-aspartate receptor 2A subunit (GRIN2A) gene suppresses transcriptional activity and correlates with chronic outcome in schizophrenia."Pharmacogenetics. 13(5). 271-278 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toyota T. et al.: "Analysis of a cluster of polymorphisms in AKT1 gene in bipolar pedigrees : a family-based association study."Neuroscience Letters. 339(1). 5-8 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwayama-Shigeno Y. et al.: "Distribution of haplotypes derived from three common variants of the NR4A2 gene in Japanese patients with schizophrenia."American Journal of Medical Genetics. 118B(1). 20-24 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ebihara M. et al.: "Transcriptional activities of cholecystokinin promoter haplotypes and their relevance to panic disorder susceptibility."American Journal of Medical Genetics. 118B(1). 32-35 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ebihara M. et al.: "Search for the causative gene in benign adult familial myoclonic epilepsy (BAFME)."Ann.ReJpn.Epi.Res.Found.. 15. 57-64 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohtsuki T. et al.: "Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees."Molecular Psychiatry. 7(9). 954-961 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toyota T. et al.: "Association analysis of adenylate cyclase type 9 gene using pedigree disequilibrium test in bipolar disorder."Molecular Psychiatry. 7(5). 450-452 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hattori E. et al.: "Association study of the short tandem repeat in the 5' upstream region of the cholecystokinin gene with mood disorders in the Japanese population."American Journal of Medical Genetics. 114(5). 523-526 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toyota T. et al.: "Molecular analysis, mutation screening, and association study of adenylate cyclase type 9 gene (ADCY9) in mood disorders."American Journal of Medical Genetics. 114(1). 84-92 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada K. et al.: "Family-based association analyses of chromosome 18 markers in schizophrenic pedigrees : comparison of the available software packages, practical guidelines for the application and interpretation of results."Brain Science and Mental Disorders. 13(3). 305-315 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshikawa T. et al.: "Progress in genetic studies on functional psychosis. (The present understanding and problems on brain research (Nou kagaku kenkyu no genjou to kadai))"Gihou. 324 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada K, et al.: "Family-based association study of schizophrenia with 444 markers and analysis of a new susceptibility locus mapped to 11q13.3."American journal of Medical Genetics (Neuropsychiatric Genetics). (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Toyota T, Yoshitsugu K, Ebihara M, Yamada K, et al.: "Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B."Human Molecular Genetics. 13(5). 551-561 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Horiuchi Y, Nakayama J, Ishiguro H, Ohtsuki T, Detera-Wadleigh SD, Toyota T, Yamada K, et al.: "Possible association between a haplotype of the GABA-A receptor alpha 1 subunit gene (GABRA1) and mood disorders"Biological Psychiatry. 55(1). 40-45 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada K, et al.: "Evidence of association between gamma-aminobutyric acid type A receptor genes located on 5q34 and female patients with mood disorders."Neuroscience Letters. 349(1). 9-12 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M Kikuchi, K Yamada, et al.: "Two-step association analyses of the chromosome 18p11.2 region in schizophrenia detect a locus encompassing C18orf1"Molecular Psychiatry. 8(5). 467-469 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Itokawa M, Yamada K, et al.: "Genetic analysis of a functional GRIN2A promoter (GT)n repeat in bipolar disorder pedigrees in humans"Neuroscience Letters. 345(1). 53-56 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Itokawa M, Yamada K, et al.: "A microsatellite repeat in the promoter of the NMDA receptor 2A subunit (GRIN2A) gene suppresses transcriptional activity and correlates with chronic outcome in schizophrenia."Pharmacogenetics. 13(5). 271-278 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Toyota T, Yamada K, et al.: "Analysis of a cluster of polymorphisms in AKT1 gene in bipolar pedigrees : a family-based association study."Neuroscience Letters. 339(1). 5-8 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iwayama-Shigeno Y, Yamada K, et al.: "Distribution of haplotypes derived from three common variants of the NR4A2 gene in Japanese patients with schizophrenia."American Journal of Medical Genetics (Neuropsychiatric Genetics). 118B(1). 20-24 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arinami T, Ishiguro H, Minowa Y, Ohtsuki T, Tsujita T, Imamura A, Yoshikawa T, Toyota T, Yamada K, et al.: "Initial genome-wide scan for linkage with schizophrenia in the Japanese schizophrenia sib-pair linkage group (JSSLG) families."American Journal of Medical Genetics (Neuropsychiatric Genetics). 120B(1). 22-28 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ebihara M, Ohba H, Hattori E, Yamada K, et al.: "Transcriptional activities of cholecystokinin promoter haplotypes and their relevance to panic disorder susceptibility."American Journal of Medical Genetics (Neuropsychiatric Genetics). 118B(1). 32-35 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 吉川武男, 糸川昌成, 山田和男: "機能性精神疾患の遺伝子研究の進歩:機能的精神疾患の系統的遺伝子解析.In:脳科学研究の現状と課題:脳とこころの病気の解明はここまで進んだ(精神・神経科学振興財団監修, 杉田秀夫, 高橋清久編集)"じほう. 324(53-69) (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kikuchi M, Yamada K, et al.: "Two-step association analyses of the chromosome 18p11.2 region in schizophrenia detect a locus encompassing C18orfl"Molecular Psychiatry. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwayama-Shigeno Y., Yamada K, et al.: "Distribution of haplotypes derived from three common variants of the NR4A2 gene in Japanese patients with schizophrenia"American Journal of Medical Genetics. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ebihara M, Ohba H, Hattori E, Yamada K, Yoshikawa T: "Transcriptional activities of cholecystokinin promoter haplotypes and their relevance to panic disorder susceptibility"American Journal of Medical Genetics. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohtsuki T, Ishiguro H, Detera-Wadleigh SD, Toyota T, Shimizu H, Yamada K, et al.: "Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees"Molecular Psychiatry. 7・9. 954-961 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Toyota T, Yamada K, et al.: "Association analysis of adenylate cyclase type 9 gene using pedigree disequilibrium test in bipolar disorder"Molecular Psychiatry. 7・5. 450-452 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hattori E, Yamada K, et al.: "Association study of the short tandem repeat in the 5' upstream region of the cholecystokinin gene with mood disorders in the Japanese population"American Journal of Medical Genetics. 114・5. 523-526 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Toyota T, Hattori E, Meerabux J, Yamada K, et al.: "Molecular analysis, mutation screening, and association study of adenylate cyclase type 9 gene(ADCY9)in mood disorders."American Joumal of Medical Genetics. 114・1. 84-2002 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山田和男: "精神分裂病家系を用いた染色体18番の疾患感受性座位の同定-伝達連鎖不平衡テストによる遺伝統計学的処理の比較-"脳と精神の医学. 13・3. 305-315 (2002)

    • Related Report
      2002 Annual Research Report

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

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