Genome-wide analysis of copy number variants in schizophrenia

• Project/Area Number: 22390223
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Nagoya University
• Principal Investigator: OZAKI Norio 名古屋大学, 医学系研究科, 教授 (40281480)
• Co-Investigator(Renkei-kenkyūsha): KAIBUCHI Kozo 名古屋大学, 大学院・医学系研究科, 教授 (00169377) ; IWATA Nakao 藤田保健衛生大学, 医学部, 教授 (60312112)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2011: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2010: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 統合失調症 / ゲノム / コピー数多型 / 神経発達 / CNV / コピー数変異

Research Abstract

We have performed high resolution genome wide copy number (CNV) screening of Japanese schizophrenic patients. Besides the known large CNVs that are previously reported to be associated with schizophrenia, we found novel variations. Smaller CNVs were followed up using lymphoblastoid cell lines (LCL) in order to measure expressional impact. No association between VIPR2duplication and schizophrenia was identified. In conclusion, our study demonstrated that combination of high resolution CNV screening and transcriptomics is useful methodfor investigating genetic susceptibility to schizophrenia.

Research Products

• [Journal Article] DPP6 as a candidate gene for neuroleptic-induced tardive dyskinesia (2013)
  • Author(s): Tanaka S, Syu A, Ishiguro H, Inada T, Horiuchi Y, Ishikawa M, Koga M, Noguchi E, Ozaki N, Someya T, Kakita A, Takahashi H, Nawa H,Arinami T
  • Journal Title: Pharmacogenomics J Volume: 13(1) Issue: 1 Pages: 27-34
  • DOI: 10.1038/tpj.2011.36
  • Peer Reviewed
• [Journal Article] Association of SNPs linked to increased expression of SLC1A1 with schizophrenia (2012)
  • Author(s): Horiuchi Y, Iida S, Koga M, Ishiguro H, Iijima Y, Inada T, Watanabe Y, Someya T, Ujike H, Iwata N, Ozaki N, Kunugi H, Tochigi M, Itokawa M, Arai M, Niizato K, Iritani S, Kakita A, Takahashi H, Nawa H, Arinami T
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet Volume: 159B(1) Issue: 1 Pages: 30-37
  • DOI: 10.1002/ajmg.b.31249
  • Peer Reviewed
• [Journal Article] Serotonin 6 receptor gene and schizophrenia: case-control study and meta-analysis (2012)
  • Author(s): Kishi T, Fukuo Y, Okochi T, Kawashima K, Kitajima T, Inada T, Ozaki N, Musso GM, Kane JM, Correll CU, Iwata N
  • Journal Title: Hum Psychopharmacol Volume: 27(1) Pages: 63-69
  • Peer Reviewed
• [Journal Article] No associations found between the genes situated at 6p22.1, HIST1H2BJ, PRSS16, and PGBD1 in Japanese patients diagnosed with schizophrenia (2012)
  • Author(s): Kitazawa M, Ohnuma T, Takebayashi Y, Shibata N, Baba H, Ohi K, Yasuda Y, Nakamura Y, Aleksic B, Yoshimi A, Okochi T, Ikeda M, Naitoh H, Hashimoto R, Iwata N, Ozaki N, Takeda M, Arai H
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet Volume: 159B(4) Issue: 4 Pages: 456-464
  • DOI: 10.1002/ajmg.b.32049
  • Peer Reviewed
• [Journal Article] Common Variants in MAGI2 Gene Are Associated with Increased Risk for Cognitive Impairment in Schizophrenic Patients (2012)
  • Author(s): Koide T, Banno M, Aleksic B, Yamashita S, Kikuchi T, Kohmura K, Adachi Y, Kawano N, Kushima I, Nakamura Y, Okada T, Ikeda M, Ohi K, Yasuda Y, Hashimoto R, Inada T, Ujike H, Iidaka T, Suzuki M, Takeda M, Iwata N, Ozaki N
  • Journal Title: PLoS One Volume: 7(5) Issue: 5 Pages: e36836-e36836
  • DOI: 10.1371/journal.pone.0036836
  • Peer Reviewed
• [Journal Article] Resequencing and Association Analysis of the KALRN and EPHB1 Genes And Their Contribution to Schizophrenia Susceptibility (2012)
  • Author(s): Kushima I, Nakamura Y, Aleksic B, Ikeda M, Ito Y, Shiino T, Okochi T, Fukuo Y, Ujike H, Suzuki M, Inada T, Hashimoto R, Takeda M, Kaibuchi K, Iwata N, Ozaki N
  • Journal Title: Schizophr Bull Volume: 38(3) Issue: 3 Pages: 552-560
  • DOI: 10.1093/schbul/sbq118
  • Peer Reviewed
• [Journal Article] An evaluation of polymorphisms in casein kinase 1 delta and epsilon genes in major psychiatric disorders (2012)
  • Author(s): Matsunaga S, Ikeda M, Kishi T, Fukuo Y, Aleksic B, Yoshimura R, Okochi T, Yamanouchi Y, Kinoshita Y, Kawashima K, Umene-Nakano W, Inada T, Kunugi H, Kato T, Yoshikawa T, Ujike H, Nakamura J, Ozaki N, Kitajima T, Iwata N
  • Journal Title: Neurosci Lett Volume: 529(1) Issue: 1 Pages: 66-69
  • DOI: 10.1016/j.neulet.2012.08.070
  • Peer Reviewed
• [Journal Article] Functional genetic variation at the NRGN gene and schizophrenia: Evidence from a gene-based case-control study and gene expression analysis (2012)
  • Author(s): Ohi K, Hashimoto R, Yasuda Y, Fukumoto M, Yamamori H, Umeda-Yano S, Okada T, Kamino K, Morihara T, Iwase M, Kazui H, Numata S, Ikeda M, Ohnuma T, Iwata N, Ueno S, Ozaki N, Ohmori T, Arai H, Takeda M
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet Volume: 159B(4) Issue: 4 Pages: 405-413
  • DOI: 10.1002/ajmg.b.32043
  • Peer Reviewed
• [Journal Article] Effects of aging on the morphologies of Heschl's gyrus and the superior temporal gyrus in schizophrenia: A postmortem study (2012)
  • Author(s): Torii Y, Iritani S, Sekiguchi H, Habuchi C, Hagikura M, Arai T, Ikeda K, Akiyama H, Ozaki N
  • Journal Title: Schizophr Res Volume: 134(2-3) Issue: 2-3 Pages: 137-142
  • DOI: 10.1016/j.schres.2011.10.024
  • Peer Reviewed
• [Journal Article] A two-stage case-control association study between the tryptophan hydroxylase 2 (TPH2) gene and schizophrenia in a Japanese population (2012)
  • Author(s): Watanabe Y, Egawa J, Iijima Y, Nunokawa A, Kaneko N, Shibuya M, Arinami T, Ujike H, Inada T, Iwata N, Tochigi M, Kunugi H, Itokawa M, Ozaki N, Hashimoto R, Someya T
  • Journal Title: Schizophr Res Volume: 137(1-3) Issue: 1-3 Pages: 264-266
  • DOI: 10.1016/j.schres.2012.01.034
  • Peer Reviewed
• [Journal Article] Serotonin 6 receptor gene and schizophrenia: case-control study and meta-analysis. (2012)
  • Author(s): Kishi T, Fukuo Y, Okochi T, Kawashima K, Kitajima T, Inada T, Ozaki N, Musso GM, Kane JM, Correll CU, Iwata N
  • Journal Title: Hum Psychopharmacol Volume: 27 (1) Pages: 63-69
  • Peer Reviewed
• [Journal Article] Loss of Function Studies in Mice and Genetic Association Link Receptor Protein Tyrosine (2011)
  • Author(s): Takahashi N, Nielsen KS, Aleksic B, Petersen S,Ikeda M, Kushima I, Vacaresse N, Ujike H, IwataN, Dubreuil V, Mirza N, Sakurai T, Ozaki N,Buxbaum JD, Sap J
  • Journal Title: Phosphatase alpha to Schizophrenia Volume: 70 (7) Issue: 7 Pages: 626-635
  • DOI: 10.1016/j.biopsych.2011.06.016
  • Peer Reviewed
• [Journal Article] Impairment of the tyrosine hydroxylase neuronal network in the orbitofrontal cortex of a genetically (2011)
  • Author(s): Sekiguchi H, Iritani S, Habuchi C, Torii Y,Kuroda K, Kaibuchi K, Ozaki N
  • Journal Title: modified mouse model of schizophrenia Volume: 1392 Pages: 47-53
  • DOI: 10.1016/j.brainres.2011.03.058
  • Peer Reviewed
• [Journal Article] Vulnerability in early life to changes in the rearing environment plays a crucial role in the aetiopathology of psychiatric disorders (2011)
  • Author(s): Niwa M, Matsumoto Y, Mouri A, Ozaki N, Nabeshima T
  • Journal Title: Int J Neuropsychopharmacol. Volume: 14(4) Issue: 04 Pages: 459-77
  • DOI: 10.1017/s1461145710001239
  • NAID: 10030656981
  • Peer Reviewed
• [Journal Article] Genome-wide association study of schizophrenia in a Japanese population (2011)
  • Author(s): Ikeda M, Aleksic B, その他20名, Ozaki N,O'Donovan MC, Iwata N
  • Journal Title: Biol Psychiatry Volume: 69 (5) Issue: 5 Pages: 472-478
  • DOI: 10.1016/j.biopsych.2010.07.010
  • Peer Reviewed
• [Journal Article] Gene-wide associationstudy between the methylenetetrahydrofolate reductase gene (MTHFR) and schizophrenia in the Japanese population, with an updated meta-analysis on currently available data (2010)
  • Author(s): Yoshimi A, et al
  • Journal Title: Schizophr Re Volume: 124 (1-3) Issue: 1-3 Pages: 216-222
  • DOI: 10.1016/j.schres.2010.07.011
  • Peer Reviewed
• [Journal Article] Diagnostic classification of schizophrenia by neural network analysis of blood-based gene expression signatures (2010)
  • Author(s): Takahashi M, et al
  • Journal Title: Schizophr Res Volume: 119 (1-3) Issue: 1-3 Pages: 210-218
  • DOI: 10.1016/j.schres.2009.12.024
  • Peer Reviewed
• [Journal Article] Association of the HSPG2 gene with neuroleptic-induced tardive Dyskinesia (2010)
  • Author(s): Syu A, et al
  • Journal Title: Neuropsychopharmacology Volume: 35 (5) Issue: 3 Pages: 1155-1164
  • DOI: 10.1038/jhg.2009.139
  • Peer Reviewed
• [Journal Article] Association study of ubiquitin-specific peptidase 46 (USP46) with bipolar disorder and schizophrenia in a Japanese population (2010)
  • Author(s): Kushima I, et al
  • Journal Title: J Hum Genet Volume: 55 (3) Issue: 7 Pages: 133-136
  • DOI: 10.1038/jhg.2010.38
  • Peer Reviewed
• [Journal Article] Supportive evidence for reduced expression of GNB1L in schizophrenia (2010)
  • Author(s): Ishiguro H, et al
  • Journal Title: Schizophr Bull Volume: 36 (4) Issue: 4 Pages: 756-765
  • DOI: 10.1093/schbul/sbn160
  • Peer Reviewed
• [Journal Article] Brain cannabinoid CB2 receptor in schizophrenia (2010)
  • Author(s): Ishiguro H, et al
  • Journal Title: Biol Psychiatry Volume: 67(10) Issue: 10 Pages: 974-982
  • DOI: 10.1016/j.biopsych.2009.09.024
  • 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, et al
  • Journal Title: Biol Psychiatry Volume: 67 (3) Issue: 3 Pages: 263-9
  • DOI: 10.1016/j.biopsych.2009.08.030
  • Peer Reviewed
• [Journal Article] Copy number variation in schizophrenia in the Japanesepopulation (2010)
  • Author(s): Ikeda M, et al
  • Journal Title: Biol Psychiatry Volume: 67 (3) Issue: 3 Pages: 283-6
  • DOI: 10.1016/j.biopsych.2009.08.034
  • Peer Reviewed
• [Journal Article] Genetic association study of KREMEN1 and DKK1 and schizophrenia in a Japanese population (2010)
  • Author(s): Aleksic B, et al
  • Journal Title: Schizophr Res Volume: 118 (1-3) Issue: 1-3 Pages: 113-7
  • DOI: 10.1016/j.schres.2010.01.014
  • Peer Reviewed
• [Journal Article] Genetic association study of KREMEN1 and DKK1 and schizophrenia in a Japanese population. (2010)
  • Author(s): Aleksic B, et al.
  • Journal Title: Schizophr Res Volume: 118(1-3) Pages: 113-7
  • Peer Reviewed
• [Journal Article] Copy number variation in schizophrenia in the Japanese population. (2010)
  • Author(s): Ikeda M, et al.
  • Journal Title: Biol Psychiatry Volume: 67(3) Pages: 283-6
  • 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, et al.
  • Journal Title: Biol Psychiatry Volume: 67(3) Pages: 263-9
  • Peer Reviewed
• [Journal Article] Brain cannabinoid CB2 receptor in schizophrenia. (2010)
  • Author(s): Ishiguro H, et al.
  • Journal Title: Biol Psychiatry Volume: 67(10) Pages: 974-82
  • Peer Reviewed
• [Journal Article] supportive evidence for reduced expression of GNB1L in schizophrenia. (2010)
  • Author(s): Ishiguro H, et al.
  • Journal Title: Schizophr Bull Volume: 36(4) Pages: 756-65
  • Peer Reviewed
• [Journal Article] A two-stage case-control association study of the dihydropyrimidinase-like 2 gene (DPYSL2) with schizophrenia in Japanese subjects. (2010)
  • Author(s): Koide T, et al.
  • Journal Title: J Hum Genet Volume: 55(7) Pages: 469-72
  • Peer Reviewed
• [Journal Article] Association study of bromodomain-containing 1 gene with schizophrenia in Japanese population. (2010)
  • Author(s): Kushima I, et al.
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet Volume: 153B(3) Pages: 786-91
  • Peer Reviewed
• [Journal Article] Association study of ubiquitin-specific peptidase 46(USP46) with bipolar disorder and schizophrenia in a Japanese population. (2010)
  • Author(s): Kushima I, et al.
  • Journal Title: J Hum Genet Volume: 55(3) Pages: 133-6
  • Peer Reviewed
• [Journal Article] Association of the HSPG2 gene with neuroleptic-induced tardive Dyskinesia. (2010)
  • Author(s): Syu A, et al.
  • Journal Title: Neuropsychopharmacology Volume: 35(5) Pages: 1155-64
  • Peer Reviewed
• [Journal Article] Diagnostic classification of schizophrenia by neural network analysis of blood-based gene expression signatures. (2010)
  • Author(s): Takahashi M, et al.
  • Journal Title: Schizophr Res Volume: 119(1-3) Pages: 210-218
  • Peer Reviewed
• [Journal Article] Gene-wide association study between the methylenetetrahydrofolatereductase gene (MTHFR) and schizophrenia in the JapaneSe population, with an updated meta-analysis on currently available data. (2010)
  • Author(s): Yoshimi A, et al.
  • Journal Title: Schizophr Res Volume: 124(1-3) Pages: 216-22
  • Peer Reviewed
• [Presentation] Myelin-related abnormality of schizophrenia: genetic, imaging and postmortem study (2012)
  • Author(s): Ozaki N
  • Organizer: the 15th Pacific Rim College of Psychiatrists Scientific Meeting (PRCP 2012) Symposium Genetics of Schizophrenia
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2012-10-25
• [Presentation] Myelin-related abnormality of schizophrenia: genetic, imaging and postmortem study. (2012)
  • Author(s): Ozaki N
  • Organizer: the 15th Pacific Rim College of Psychiatrists Scientific Meeting (PRCP 2012) Symposium Genetics of Schizophrenia
  • Place of Presentation: Seoul, Korea
  • Invited
• [Presentation] Protein tyrosine phosphatase alufa as novel candidate molecule for the etiopathology of schizophrenia: Genetic analysis and biological implications (2011)
  • Author(s): 尾崎紀夫
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-16
• [Presentation] Protein tyrosine phosphatase alufa as novel candidate molecule for the etiopathology of schizophrenia : Genetic analysis and biological implications (2011)
  • Author(s): 尾崎紀夫
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-16
• [Presentation] Genome study of Japanese schizophrenia: GWAS, CNV and Rare variants: Symposium: Neuroscience and neurochemistry in Japan (2011)
  • Author(s): Ozaki N
  • Organizer: WFSBP Congress 2011
  • Place of Presentation: Prague
  • Year and Date: 2011-05-31
• [Presentation] Genome study of Japanese schizophrenia : GWAS, CNV and Rare variants : Symposium : Neuroscience and neurochemistry in Japan (2011)
  • Author(s): Ozaki N
  • Organizer: WFSBP Congress 2011
  • Place of Presentation: Prague(チェコ共和国)
  • Year and Date: 2011-05-31
• [Patent(Industrial Property Rights)] 統合失調症マーカー及びその利用 (2010)
  • Inventor(s): 尾崎紀夫, 永井拓, 吉見陽, 山田真之亮
  • Industrial Property Rights Holder: 国立大学法人名古屋大学
  • Filing Date: 2010-06-29