Treatment intervention pathway analysis of genes associated with schizophrenia

• Project/Area Number: 20390098
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: University of Tsukuba
• Principal Investigator: ARINAMI Tadao University of Tsukuba, 大学院・人間総合科学研究科, 教授 (10212648)
• Co-Investigator(Kenkyū-buntansha): 石黒 浩毅 筑波大学, 大学院・人間総合科学研究科, 講師 (20375489)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000); Fiscal Year 2010: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: ゲノム医科学 / 遺伝子 / 脳神経疾患 / 薬剤反応性 / ゲノム

Research Abstract

The purpose of this study is to identify candidate genes of treatment target for schizophrenia. We searched for genes associated with schizophrenia by genome-wide association methods in Japanesepopulations. Among the potentially associated genes identified, we focused on the SMARCA2 gene because psychotogenic drugs lowered Smarca2 expression while antipsychotic drugs increased it in the mouse brain. Furthermore, we found constant expression of Homer1a isoform in Smarca2 knockout mice. The findings of this study indicate that decreased function of SMRACA2 is involved in schizophrenia through glutamatergic synaptic transmission dysfunction and the SMARCA2 gene genotypes might be potential information of personalized medicine in choice of treatment of schizophrenia.

Research Products

• [Journal Article] Functional polymorphism in the GPR55 gene is associated with anorexia nervosa. (2011)
  • Author(s): Ishiguro H, Onaivi ES, Horiuchi Y, Imai K, Komaki G, Ishikawa T, Suzuki M, Watanabe Y, Ando T, Higuchi S, Arinami T.
  • Journal Title: Synapse 65(2) Pages: 103-108
  • Peer Reviewed
• [Journal Article] Methylenetetrahydrofolate reductase(MTHFR)C677T and A 1298C polymorphisms and age of onset in schizophrenia : A combined analysis ofindependent samples. (2011)
  • Author(s): Saetre P, Vares M, Werge T, Andreassen OA, Arinami T, Ishiguro H, Nanko S, Tan EC, HanDH, Roffman JL, Muntjewerff JW, Jagodzinski PP, Kempisty B, Hauser J, Vilella E, Betcheva E, Nakamura Y, Regland B, Agartz I, Hall H, Terenius L, Jonsson EG.
  • Journal Title: American Journal of Medical Genetics B(Neuropsychiatric Genetics) Volume: 156 Pages: 215-224
  • Peer Reviewed
• [Journal Article] An association study between the dymeclin gene and schizophrenia in the Japanese population. (2010)
  • Author(s): Yazaki S, Koga M, Ishiguro H, Inada T, Ujike H, Itokawa M, Otowa T, Watanabe Y, Someya T, Iwata N, Kunugi H, Ozaki N, Arinami T.
  • Journal Title: J Hum Genet. 55(9) Pages: 631-634
  • NAID: 10030736885
  • Peer Reviewed
• [Journal Article] Functional polymorphism in the GPR55 gene is associated with anorexia nervosa. (2010)
  • Author(s): Ishiguro H, Onaivi ES, Horiuchi Y, Imai K, Komaki G, Ishikawa T, Suzuki M, Watanabe Y, Ando T, Higuchi S, Arinami T.
  • Journal Title: Synapse e-pub
  • Peer Reviewed
• [Journal Article] Replication study of association between ADCYAP1 gene polymorphisms and schizophrenia. (2010)
  • Author(s): Koga M, Ishiguro H, Horiuchi Y, Inada T, Ujike H, Itokawa M, Otowa T, Watanabe Y, Someya T, Arinami T.
  • Journal Title: Psychiatr Genet. 20(3) Pages: 123-125
  • Peer Reviewed
• [Journal Article] Association of the HSPG2 gene with neuroleptic-induced tardive dyskinesia (2010)
  • Author(s): Syu A, Ishiguro H, Inada T, Horiuchi Y, Tanaka S, Ishikawa M, Arai M, Itokawa M, Niizato K, Iritani S, Ozaki N, Takahashi M, Kakita A, Takahashi H, Nawa H, Keino-Masu K, Arikawa-Hirasawa E, Arinami T.
  • Journal Title: Neuropsychopharmacology. 35(5) Pages: 1155-1164
  • Peer Reviewed
• [Journal Article] Brain cannabinoid CB2 receptor in schizophrenia. (2010)
  • Author(s): Ishiguro H, Horiuchi Y, Ishikawa M, Koga M, Imai K, Suzuki Y, Morikawa M, Inada T, Watanabe Y, Takahashi M, Someya T, Ujike H, Iwata N, Ozaki N, Onaivi ES, Kunugi H, Sasaki T, Itokawa M, Arai M, Niizato K, Iritani S, Naka I, Ohashi J, Kakita A, Takahashi H, Nawa H, Arinami T.
  • Journal Title: Biol Psychiatry. 67(10) Pages: 974-982
  • Peer Reviewed
• [Journal Article] A nonsynonymous polymorphism in cannabinoid CB2 receptor gene is associated with eating disorders in humans and food intake is modified in mice by its ligands. (2010)
  • Author(s): Ishiguro H, Carpio O, Horiuchi Y, Shu A, Higuchi S, Schanz N, Benno R, Arinami T, Onaivi ES
  • Journal Title: Synapse 64(1) Pages: 92-96
  • Peer Reviewed
• [Journal Article] Identification of novel candidate genes for treatment response to risperidone and susceptibility for schizophrenia : integrated analysis among pharmacogenomics, mouse expression, and genetic case-control association approaches. (2010)
  • Author(s): Ikeda M, Tomita Y, Mouri A, Koga M, Okochi T, Yoshimura R, Yamanouchi Y, Kinoshita Y, Hashimoto R, Williams HJ, Takeda M, Nakamura J, Nabeshima T, Owen MJ, O'Donovan MC, Honda H, Arinami T, Ozaki N, Iwata N.
  • Journal Title: Biological Psychiatry Volume: 67 Pages: 263-269
  • Peer Reviewed
• [Journal Article] The dopamine D3 receptor (DRD3) gene and risk of schizophrenia : case-control studies and an updated meta-analysis. (2010)
  • Author(s): Nunokawa A, Watanabe Y, Kaneko N, Sugai T, Yazaki S, Arinami T, Ujike H, Inada T, Iwata N, Kunugi H, Sasaki T, Itokawa M, Ozaki N, Hashimoto R, Someya T.
  • Journal Title: Schizophrenia Research Volume: 116 Pages: 61-67
  • Peer Reviewed
• [Journal Article] Brain cannabinoid CB2 receptor in schizophrenia. (2010)
  • Author(s): Ishiguro H, Horiuchi Y, Ishikawa M, Koga M, Imai K, Suzuki Y, Morikawa M, Inada T, Watanabe Y, Takahashi M, Someya T, Ujike H, Iwata N, Ozaki N, Onaivi ES, Kunugi H, Sasaki T, Itokawa M, Arai M, Niizato K, Iritani S, Naka I, Ohashi J, Kakita A, Takahashi H, Nawa H, Arinami T.
  • Journal Title: Biological Psychiatry Volume: 67 Pages: 974-982
  • Peer Reviewed
• [Journal Article] Association of the HSPG2 gene with neuroleptic-induced tardive dyskinesia. (2010)
  • Author(s): Syu A, Ishiguro H, Inada T, Horiuchi Y, Tanaka S, Ishikawa M, Arai M, Itokawa M, Niizato K, Iritani S, Ozaki N, Takahashi M, Kakita A, Takahashi H, Nawa H, Keino-Masu K, Arikawa-Hirasawa E, Arinami T
  • Journal Title: Neuropsychopharmacology Volume: 35 Pages: 1155-1164
  • Peer Reviewed
• [Journal Article] Failure to find an association between myosin heavy chain 9, non-muscle(MYH9)and schizophrenia : a three-stage case control association study. (2010)
  • Author(s): Amagane H, Watanabe Y, Kaneko N, Nunokawa A, Muratake T, Ishiguro H, Arinami T, Ujike H, Inada T, Iwata N, Kunugi H, Sasaki T, Hashimoto R, Itokawa M, Ozaki N, Someya T.
  • Journal Title: Schiozophrenia Research Volume: 118 Pages: 106-112
  • Peer Reviewed
• [Journal Article] Replication study of association between ADCYAP I gene polymorphisms and schizophrenia. (2010)
  • Author(s): Koga M, Ishiguro H, Horiuchi Y, Inada T, Ujike H, Itokawa M, Otowa T, Watanabe Y, Someya T, Arinami T.
  • Journal Title: Psychiatric Genetics Volume: 20 Pages: 123-125
  • Peer Reviewed
• [Journal Article] An association study between the dymeclin gene and schizophrenia in theJapanese population. (2010)
  • Author(s): Yazaki S, Koga M, Ishiguro H, Inada T, Ujike H, Itokawa M, Otowa T, Watanabe Y, Someya T, Iwata N, Kunugi H, Ozaki N, Arinami T.
  • Journal Title: Journal of Human Genetics Volume: 55 Pages: 631-634
  • Peer Reviewed
• [Journal Article] Advanced research on dopamine signaling to develop drugs for the treatment of mental disorders : Ser311Cys polymorphisms of the dopamine D2-receptorgene and schizophrenia. (2010)
  • Author(s): Itokawa M, Arinami T, Toru M.
  • Journal Title: Journal of Pharmacological Sciences Volume: 67 Pages: 974-982
  • Peer Reviewed
• [Journal Article] Association of the HSPG2 gene with neuroleptic-induced tardive Dyskinesia. (2010)
  • Author(s): Syu A, Ishiguro H, Inada T, Horiuchi Y, Tanaka S, Ishikawa M, Arai M, Itokawa M, Niizato K, Iritani S, Ozaki N, Takahashi M, Kakita A, Takahashi H, Nawa H, Keino-Masu K, Arikawa-Hirasawa E, Arinami T.
  • Journal Title: Neuropsychopharmacology 35 Pages: 1155-1164
  • Peer Reviewed
• [Journal Article] The dopamine D3 receptor(DRD3)gene and risk of schizophrenia : casecontrol studies and an updated meta-analysis. (2010)
  • Author(s): Nunokawa A, Watanabe Y, Kaneko N, Sugai T, Yazaki S, Arinami T, Ujike H, Inada T, Iwata N, Kunugi H, Sasaki T, Itokawa M, Ozaki N, Hashimoto R, Someya T
  • Journal Title: Schizophr Research 116 Pages: 61-67
  • Peer Reviewed
• [Journal Article] Identification of novel candidate genes for treatment response to risperidone and susceptibility for schizophrenia : integrated analysis among pharmacogenomics, mouse expression, and genetic case-control association approaches. (2010)
  • Author(s): Ikeda M, Tomita Y, Mouri A, Koga M, Okochi T, Yoshimura R, Yamanouchi Y, Kinoshita Y, Hashimoto R, Williams HJ, Takeda M, Nakamura J, Nabeshima T, Owen MJ, O'Donovan MC, Honda H, Arinami T, Ozaki N, Iwata N.
  • Journal Title: Biol Psychiatry 67 Pages: 263-269
  • Peer Reviewed
• [Journal Article] A nonsynonymous polymorphism in cannabinoid CB2 receptor gene is associated with eating disorders in humans and food intake is modified in mice by its ligands. (2010)
  • Author(s): Ishiguro H, Carpio O, Horiuchi Y, Shu A, Higuchi S, Schanz N, Benno R, Arinami T, Onaivi ES.
  • Journal Title: Synapse 64 Pages: 92-96
  • Peer Reviewed
• [Journal Article] Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia. (2009)
  • Author(s): Koga M, Ishiguro H, Yazaki S, Horiuchi Y, Arai M, Niizato K, Iritani S, Itokawa M, Inada T, Iwata N, Ozaki N, Ujike H, Kunugi H, Sasaki T, Takahashi M, Watanabe Y, Someya T, Kakita A, Takahashi H, Nawa H, Muchardt C, Yaniv M, Arinami T
  • Journal Title: Hum Mol Genet. 18(13) Pages: 2483-2494
  • Peer Reviewed
• [Journal Article] Two-stage case-control association study of polymorphisms in rheumatoid arthritis susceptibility genes with schizophrenia. (2009)
  • Author(s): Watanabe Y, Nunokawa A, Kaneko N, Muratake T, Arinami T, Ujike H, Inada T, Iwata N, Kunugi H, Itokawa M, Otowa T, Ozaki N, Someya T
  • Journal Title: Journal of Human Genetics 54 Pages: 62-65
  • NAID: 10030728996
  • Peer Reviewed
• [Journal Article] Meta-analysis of 32 genome-wide linkage studies of schizophrenia. (2009)
  • Author(s): Ng MY, Levinson DF, Faraone SV, Suarez BK, DeLisi LE, Arinami T, Lewis CM
  • Journal Title: Molecular Psychiatry 14 Pages: 774-785
  • Peer Reviewed
• [Journal Article] Species differences in cannabinoid receptor 2(CNR2 gene) : identification of novel human and rodent CB2 isoforms, differential tissue expression and regulation by cannabinoid receptor ligands. (2009)
  • Author(s): Liu QR, Pan CH, Hishimoto A, Li CY, Xi ZX, Llorente-Berzal A, Viveros MP, Ishiguro H, Arinami T, Onaivi ES, Uhl GR
  • Journal Title: Genes, brain, and behavior 8 Pages: 519-530
  • Peer Reviewed
• [Journal Article] Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia. (2009)
  • Author(s): Koga M, Ishiguro H, Yazaki S, Horiuchi Y, Arai M, Niizato K, Iritani S, Itokawa M, Inada T, Iwata N, Ozaki N, Ujike H, Kunugi H, Sasaki T, Takahashi M, Watanabe Y, Someya T, Kakita A, Takahashi H, Nawa H, Muchardt C, Yaniv M, Arinami T.
  • Journal Title: Hum Mol Genet 18 Pages: 2483-2494
  • Peer Reviewed
• [Journal Article] A two-stage case-control association study of PADI2 with schizophrenia. (2009)
  • Author(s): Watanabe Y, Nunokawa A, Kaneko N, Arinami T, Ujike H, Inada T, Iwata N, Kunugi H, Itokawa M, Otowa T, Ozaki N, Someya T.
  • Journal Title: J Hum Genet 54 Pages: 430-432
  • NAID: 10030731190
  • Peer Reviewed
• [Journal Article] Supportive evidence for reduced expression of GNB1L in schizophrenia. (2009)
  • Author(s): Ishiguro H, Koga M, Horiuchi Y, Noguchi E, Morikawa M, Suzuki Y, Arai M, Niizato K, Iritani S, Itokawa M, Inada T, Iwata N, Ozaki N, Ujike H, Kunugi H, Sasaki T, Takahashi M, Watanabe Y, Someya T, Kakita A, Takahashi H, Nawa H, Arinami T
  • Journal Title: Schizophr Bull (印刷中)
  • Peer Reviewed
• [Journal Article] Meta-analysis of 32 genome-wide linkage studies of schizophrenia (2009)
  • Author(s): Ng MY, Levinson DF, Faraone SV, Suarez BK, Delisi LE, Arinami T, 他
  • Journal Title: Mol Psychiatry
  • Peer Reviewed
• [Journal Article] Replication study and meta-analysis of the genetic association of GRM3 gene polymorphisms with schizophrenia in a large Japanese case-control population. (2008)
  • Author(s): Albalushi T, Horiuchi Y, Ishiguro H, Koga M, Inada T, Iwata N, Ozaki N, Ujike H, Watanabe Y, Someya T, Arinami T
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet 147 Pages: 392-396
  • Peer Reviewed
• [Journal Article] A polymorphism of the metabotropic glutamate receptor mGluR7 (GRM7) gene is associated with schizophrenia. (2008)
  • Author(s): Ohtsuki T, Koga M, Ishiguro H, Horiuchi Y, Arai M, Niizato K, Itokawa M, Inada T, Iwata N, Iritani S, Ozaki N, Kunugi H, Ujike H, Watanabe Y, Someya T, Arinami
  • Journal Title: Schizophr Res. 101 Pages: 9-16
  • NAID: 120007138788
  • Peer Reviewed
• [Journal Article] Pathway-based association analysis of genome-wide screening data suggest that genes associated with the gamma-aminobutyric acid receptor signaling pathway are involved in neuroleptic-induced, treatment-resistant tardive dyskinesia. (2008)
  • Author(s): Inada T, Koga M, Ishiguro H, Horiuchi Y, Syu A, YoshioT, Takahashi N, Ozaki N, Arinami T.
  • Journal Title: Phannacogenet Genomics 18 Pages: 317-323
  • Peer Reviewed
• [Journal Article] Association of PTPRB gene polymorphism with drug addiction. (2008)
  • Author(s): Ishiguro H, Gong JP, Hall FS, Arinami T, Uhl GR.
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet. 147 Pages: 1167-1172
  • Peer Reviewed
• [Journal Article] Association of polymorphisms in the haplotype block spanning.the alternatively spliced exons of the NTNG1 gene at 1p13.3 with schizophrenia in Japanese populations. (2008)
  • Author(s): Ohtsuki T, Horiuchi Y, Koga M, Ishiguro H, Inada T, Iwata N, Ozaki N, Ujike H, Watanabe Y, Someya T, Arinami T
  • Journal Title: Neurosci Lett. 435 Pages: 194-197
  • Peer Reviewed
• [Journal Article] Large-scale case-control study of a functional polymorphism in the glutamate receptor, metabotropic 3 gene in patients with schizophrenia. (2008)
  • Author(s): Nunokawa A, Watanabe Y, Kitamura H, Kaneko N, Arinami T, Ujike H, Inada T, Iwata N, Kunugi H, Itokawa M, Ozaki N, Someya T.
  • Journal Title: Psychiatry Clin Neurosci 62 Pages: 239-240
  • Peer Reviewed
• [Journal Article] Replication study for associations between polymorphisms in the CLDN5 and DGCR2 genes in the 22q11 deletion syndrome region and schizophrenia. (2008)
  • Author(s): Ishiguro H, Koga M, Horiuchi Y, Noguchi E, Morikawa M, Suzuki Y, Arai M, Niizato K, Iritani S, Itokawa M, Inada T, Iwata N, Ozaki N, Ujike H, Kunugi H, Sasaki T, Takahashi M, Watanabe Y, Someya T, Kakita A, Takahashi H, Nawa H, Arinami T
  • Journal Title: Psychiatr Genet 18 Pages: 255-256
  • Peer Reviewed
• [Journal Article] Two-stage case-control association study of polymorphisms in rheumatoid arthritis susceptibility genes with schizophrenia. (2008)
  • Author(s): Watanabe Y, Nunokawa A, Kaneko N, Muratake T, Arinami T, Ujike H, Inada T, Iwata N, Kunugi H, Itokawa M, Otowa T, Ozaki N, Someya T
  • Journal Title: J Hum Genet. 54 Pages: 62-65
  • NAID: 10030728996
  • Peer Reviewed
• [Presentation] ヒト、マウスモデルを用いたPDLIM5遺伝子の精神疾患の関連 (2010)
  • Author(s): 海東伸子
  • Organizer: 日本人類遺伝学会第55回大会
  • Place of Presentation: 大宮
  • Year and Date: 2010-10-30
• [Presentation] 薬原性遅発性ジスキネジアを表現型とした全ゲノム解析 (2010)
  • Author(s): 有波忠雄
  • Organizer: 2010日本臨床精神神経薬理学会
  • Place of Presentation: 仙台
  • Year and Date: 2010-09-15
• [Presentation] 薬原性遅発性ジスキネジアを表現型とした全ゲノム解析 (2010)
  • Author(s): 有波忠雄、石黒浩毅、稲田俊也、尾崎紀夫
  • Organizer: 第20回日本臨床精神神経薬理学会
  • Place of Presentation: 仙台
  • Year and Date: 2010-09-15
• [Presentation] MTHFR遺伝子多型と統合失調症との関連 (2010)
  • Author(s): 有波忠雄、石黒浩毅、功刀浩、佐々木司、氏家寛、染矢俊幸、渡部雄一郎、橋本亮太
  • Organizer: 第6回日本統合失調症学会
  • Place of Presentation: 福岡
  • Year and Date: 2010-03-27
• [Presentation] Demeclin遺伝子と統合失調症との関連解析 (2009)
  • Author(s): 矢崎沙織
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-26
• [Presentation] 薬原性遅発性ジスキネジアとHSPG2遺伝子との関連 (2009)
  • Author(s): 有波忠雄
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-24
• [Presentation] Large-scale genetic association study of schizophrenia. (2008)
  • Author(s): Arinami T
  • Organizer: 第51回日本神経化学会大会
  • Place of Presentation: 富山
  • Year and Date: 2008-09-02
• [Remarks] ホームページ等
  • URL: http://www.md.tsukuba.ac.jp/basic-med/m-genetics/