Omics Analysis of Schizophrenia

• Project/Area Number: 25860999
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Nagoya University
• Principal Investigator: YOSHIMI Akira 名古屋大学, 医学(系)研究科(研究院), 研究員 (00637671)
• Research Collaborator: OZAKI Norio 名古屋大学, 医学系研究科, 教授 (40281480)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 統合失調症 / 網羅的解析 / プロテオーム / トランスクリプトーム / 分子精神医学 / ゲノム医学 / バイオインフォマティクス / オミックス / ゲノム医科学

Outline of Final Research Achievements

Omics (genome, transcriptome, and proteome) analysis of lymphoblastoid cell line (LCL) derived from schizophrenia patients and healthy controls was conducted to explore the key molecules underlying the pathophysiology of schizophrenia. The subtle differences between schizophrenics and controls in gene and protein levels were detected, and they were related to the molecular mechanisms that contribute to the pathophysiology of schizophrenia. In addition, we successfully constructed logistic regression models with good discriminative ability between schizophrenics and controls and detected a number of regulatory SNPs by integrating data from genotype and expression wise analysis (expression quantitative trait loci: eQTL).

Research Products

• [Journal Article] Identification of rare, single-nucleotide mutations in NDE1 and their contributions to schizophrenia susceptibility (2015)
  • Author(s): Kimura H, Tsuboi D, Wang C, Kushima I, Koide T, Ikeda M, Iwayama Y, Toyota T, Yamamoto N, Kunimoto S, Nakamura Y, Yoshimi A, Banno M, Xing J, Takasaki Y, Yoshida M, Aleksic B, Uno Y, Okada T, Iidaka T, Inada T, Suzuki M, Ujike H, Kunugi H, Kato T, Yoshikawa T, Iwata N, Kaibuchi K
  • Journal Title: Schizophrenia Bulltein Volume: 41 Issue: 3 Pages: 744
  • DOI: 10.1093/schbul/sbu147
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association study of BCL9 gene polymorphism rs583583 with schizophrenia and negative symptoms in Japanese population. (2015)
  • Author(s): Kimura H, Tanaka S, Kushima I, Koide T, Banno M, Kikuchi T, Nakamura Y, Shiino T, Yoshimi A, Oya-Ito T, Xing J, Wang C, Takasaki Y, Aleksic B, Okada T, Ikeda M, Inada T, Iidaka T, Iwata N, Ozaki N.
  • Journal Title: Scientific reports Volume: 5 Issue: 1 Pages: 15705-15705
  • DOI: 10.1038/srep15705
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Resequencing and Association Analysis of PTPRA, a Possible Susceptibility Gene for Schizophrenia and Autism Spectrum Disorders (2014)
  • Author(s): Xing J, Wang C, Kimura H, Takasaki Y, Kunimoto S, Yoshimi A, Nakamura Y, Koide T, Banno M, Kushima I, Uno Y, Okada T, Aleksic B, Ikeda M, Iwata N, Ozaki N.
  • Journal Title: PLoS One Volume: 9 Issue: 1-3 Pages: 149-156
  • DOI: 10.1016/j.schres.2014.04.032
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Resequencing and association analysis of PTPRA, a possible susceptibility gene for schizophrenia and autism spectrum disorders (2014)
  • Author(s): Xing J, Wang C, Kimura H, Takasaki Y, Kunimoto S, Yoshimi A, Nakamura Y, Koide T, Banno M, Kushima I, Uno Y, Okada T, Aleksic B, Ikeda M, Iwata N, Ozaki N
  • Journal Title: PLoS One Volume: 9(11) Issue: 11 Pages: e112531-e112531
  • DOI: 10.1371/journal.pone.0112531
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Definition and refinement of the 7q36.3 duplication region associated with schizophrenia (2013)
  • Author(s): Aleksic B, Kushima I, Ohye T, Ikeda M, Kunimoto S, Nakamura Y, Yoshimi A, Koide T, Iritani S, Kurahashi H, Iwata N, Ozaki N
  • Journal Title: Sci Rep Volume: 3 Issue: 1 Pages: 2587-2587
  • DOI: 10.1038/srep02587
  • Peer Reviewed
• [Presentation] The development of molecular diagnostic tool for schizophrenia using lymphoblastoid cell lines. (2016)
  • Author(s): Yoshimi A, Yamada S, Kunimoto S, Aleksic B, Hirakawa A, Ohashi M, Matsumoto Y, Arioka Y, Oya-Ito T, Kushima I, Nakamura Y, Shiino T, Mori D, Maeda T, Tanaka S, Hamada S, Noma H, Yoshida M, Noda Y, Nagai T, Yamada K, and Ozaki N
  • Organizer: US HUPO 2016
  • Place of Presentation: Boston, USA
  • Year and Date: 2016-03-13
  • Int'l Joint Research
• [Presentation] Identification of rare disruptive variants in voltage-gated channnel genes (CACNA1C, CACNA1D, CACNA1S, CACNA1l) in Japanese samples of schizophrenia and autism spectrum disorder usuing lon Torrent PGM platform (2015)
  • Author(s): Wang C, Kimura H, Xing J, Kushima I, Arioka Y, Yoshimi A, Nakamura Y, Shiino T, Oya T, Takasaki Y, Uno Y, Okada T, Iidaka T, Aleksic B, Mori D, Ikeda M, Iwata N, and Ozaki N
  • Organizer: XXIIIrd World Congress of Psychiatric Genetics
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2015-10-16
  • Int'l Joint Research
• [Presentation] Mutation Screening of the PCDH15 gene in patients suffering from Autism Spectrum Disorders and Schizophrenia. (2015)
  • Author(s): Ishizuka K, Wang C, Kimura H, Xing J, Kushima I, Arioka Y, Yoshimi A, Nakamura Y, Shiino T, Oya-Ito T, Takasaki Y, Uno Y, Okada T, Mori D, Aleksic B, and Ozaki N
  • Organizer: XXIIIrd World Congress of Psychiatric Genetics
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2015-10-16
  • Int'l Joint Research
• [Presentation] Identification of rare disruptive variants in voltage-gated channnel genes (CACNA1C, CACNA1D, CACNA1S, CACNA1l) in Japanese samples of schizophrenia and autism spectrum disorder usuing lon Torrent PGM platform (2015)
  • Author(s): Wang C, Kimura H, Xing J, Kushima I, Arioka Y, Yoshimi A, Nakamura Y, Shiino T, Oya T, Takasaki Y, Uno Y, Okada T, Iidaka T, Aleksic B, Mori D, Ikeda M, Iwata N, and Ozaki N
  • Organizer: American Society of Human Genetics Annunal Meeting-ASHG2015
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2015-10-06
  • Int'l Joint Research
• [Presentation] Transcriptome analysis of lymphoblastoid cell line from schizophrenia and bipolar disorder. (2014)
  • Author(s): Akira Yoshimi, Branko Aleksic, Shohko Kunimoto, Itaru Kushima, Yukako Nakamura, Hiroki Kimura, Yuto Takasaki, Chenyao Wang, Jingrui Xing, Akihiro Hirakawa, Masashi Ikeda, Nakao Iwata, Norio Ozaki
  • Organizer: XXIInd World Congress of Psychiatric Genetics
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2014-10-12 – 2014-10-16
• [Presentation] Novel rare disruptive variants in Rho GTPase Activating Protein 10 (ARHGAP10) in schizophrenia and autism spectrum disorder. (2014)
  • Author(s): Chenyao Wang, Daisuke Tsuboi, Itaru Kushima, Shohko Kunimoto, Akira Yoshimi, Yukako Nakamura, Takayoshi Koide, Hiroki Kimura, Yuto Takasaki, Jingrui Xing, Yota Uno, Takashi Okada, Tetsuya Iidaka, Branko Aleksic, Daisuke Mori, Masashi Ikeda, Toshiya Inada, Nakao Iwata, Kozo Kaibuchi, Norio Ozaki
  • Organizer: XXIInd World Congress of Psychiatric Genetics
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2014-10-12 – 2014-10-16
• [Presentation] Mutation screening in GRIN2A and GRIN2B with Schizophrenia and Autistic Spectrum Disorder in Japanese population. (2014)
  • Author(s): Yuto Takasaki, Takayoshi Koide, Chenyao Wang, Hiroki Kimura, Shohko Kunimoto, Akira Yoshimi, Yukako Nakamura, Itaru Kushima, Jingrui Xing, Branko Aleksic, Masashi Ikeda, Nakao Iwata, Norio Ozaki
  • Organizer: XXIInd World Congress of Psychiatric Genetics
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2014-10-12 – 2014-10-16
• [Presentation] Screening, Identification, and Functional Analysis of Novel Missense Mutations in the NDE1 Gene in Japanese patients with Schizophrenia. (2014)
  • Author(s): Hiroki Kimura, Daisuke Tsuboi, Chenyao Wang, Itaru Kushima, Takayoshi Koide, Masashi Ikeda, Akira Yoshimi, Yuto Takasaki, Aleksic Branko, Hiroshi Kunugi, Tadafumi Kato, Takeo Yoshikawa, Nakao Iwata, Kozo Kaibuchi, Norio Ozaki
  • Organizer: XXIInd World Congress of Psychiatric Genetics
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2014-10-12 – 2014-10-16
• [Presentation] PROTEOMIC ANALYSIS OF THE LYMPHOBLASTOID CELL LINE DERIVED FROM JAPANESE SCHIZOPHRENIC PATIENTS. (2014)
  • Author(s): Akira Yoshimi, Shohko Kunimoto, Shinnosuke Yamada, Branko Aleksic, Akihiro Hirakawa, Taku Nagai, Norio Ozaki
  • Organizer: 29th CINP World Congress of Neuropsychopharmacology
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2014-06-22 – 2014-06-26
• [Presentation] Serotonin transporter ubiquitynation is a potential biomarker for major depressive disorder. (2014)
  • Author(s): Toshitaka Nabeshima, Akihiro Mouri, Misato Yokoyama, Naoko Kawano, Akira Yoshimi, Masashi Ikeda, Takayoshi Mamiya, Kiyofumi Yamada, Nakao Iwata, Norio Ozaki, Yukihiro Noda
  • Organizer: 29th CINP World Congress of Neuropsychopharmacology
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2014-06-22 – 2014-06-26
• [Presentation] TRANSCRIPTOME ANALYSIS OF LYMPHOBLASTOID CELL LINE IN THE JAPANESE SCHIZOPHRENIC PATIENTS (2013)
  • Author(s): Akira Yoshimi, Branko Aleksic, Shohko Kunimoto, Itaru Kushima, Yukako Nakamura, Masashi Ikeda, Nakao Iwata, Kinji Ohno, Norio Ozaki
  • Organizer: XXIst World Congress of Psychiatric Genetics
  • Place of Presentation: Boston, USA
• [Presentation] COMMON VARIANTS IN BCL9 GENE AND SCHIZOPHRENIA IN JAPANESE POPULATION: ASSOCIATION STUDY, META-ANALYSIS AND COGNITIVE FUNCTION ANALYSIS (2013)
  • Author(s): Branko Aleksic, Itaru Kushima, Shohko Kunimoto, Yukako Nakamura, Akira Yoshimi, Masashi Ikeda, Toshiya Inada, Hiroshi Ujike, Michio Suzuki, Nakao Iwata, Norio Ozaki
  • Organizer: XXIst World Congress of Psychiatric Genetics
  • Place of Presentation: Boston, USA
• [Presentation] NOVEL RARE VARIANTS IN F-BOX PROTEIN 45 (FBXO45) IN SCHIZOPHRENIA (2013)
  • Author(s): Chenyao Wang, Hiroki Kimura, Shohko Kunimoto, Akira Yoshimi, Yukako Nakamura, Itaru Kushima, Jingrui Xing, Branko Aleksic, Masashi Ikeda, Nakao Iwata, Norio Ozaki
  • Organizer: XXIst World Congress of Psychiatric Genetics
  • Place of Presentation: Boston, USA
• [Presentation] RESEQUENCING AND ASSOCIATION ANALYSIS OF THE NDE1 GENES AND ITS CONTRIBUTION TO NEUROPSYCHIATRIC DISEASE SUSCEPTIBILITY (2013)
  • Author(s): Hiroki Kimura, Daisuke Tsuboi, Wang Chenyao, Takayoshi Koide, Itaru Kushima, Akira Yoshimi, Xing Jingrui, Shohko Kunimoto, Branko Aleksic, Kozo Kaibuchi, Norio Ozaki
  • Organizer: XXIst World Congress of Psychiatric Genetics
  • Place of Presentation: Boston, USA
• [Presentation] THE SEARCH FOR ADDITIONAL VARIANTS RESPONSIBLE FOR PHENOTYPIC VARIABILITY OF 22Q11.21 DELETION SYNDROME (2013)
  • Author(s): Itaru Kushima, Branko Aleksic, Chenyao Wang, Hiroki Kimura, Shohko Kunimoto, Akira Yoshimi, Yukako Nakamura, Jingrui Xing, Norio Ozaki
  • Organizer: XXIst World Congress of Psychiatric Genetics
  • Place of Presentation: Boston, USA
• [Presentation] RESEQUENCING AND ASSOCIATION ANALYSIS OF PTPRA AS A POSSIBLE SUSCEPTIBILITY GENE FOR SCHIZOPHRENIA (2013)
  • Author(s): Jingrui Xing, Chenyao Wang, Hiroki Kimura, Shohko Kunimoto, Akira Yoshimi, Yukako Nakamura, Itaru Kushima, Branko Aleksic, Masashi Ikeda, Nakao Iwata, Norio Ozaki
  • Organizer: XXIst World Congress of Psychiatric Genetics
  • Place of Presentation: Boston, USA
• [Remarks] 名古屋大学大学院医学系研究科精神医学分野ホームページ「研究内容」
  • URL: http://www.med.nagoya-u.ac.jp/seisin/graduateschool/research.html#h4-4-4
• [Remarks] 名古屋大学大学院医学系研究科・医学部医学科 脳神経病態制御学 精神医学／精神生物学HP
  • URL: http://www.med.nagoya-u.ac.jp/medical/6391/6404/seishinigaku_seishinseibutsugaku.html
• [Remarks] 名古屋大学医学部附属病院精神科・親と子どもの心療科HP
  • URL: http://www.med.nagoya-u.ac.jp/seisin/graduateschool/research.html
• [Remarks] 名古屋大学大学院医学系研究科・医学部医学科 脳神経病態制御学 精神医学／精神生物学 ホームページ
  • URL: http://www.med.nagoya-u.ac.jp/medical/6391/6404/seishinigaku_seishinseibutsugaku.html
• [Remarks] 名古屋大学医学部附属病院精神科・親と子どもの心療科 ホームページ
  • URL: http://www.med.nagoya-u.ac.jp/seisin/graduateschool/research.html
• [Patent(Industrial Property Rights)] 統合失調症マーカーセット及びその利用 (2013)
  • Inventor(s): 尾崎紀夫,永井拓,吉見陽,他
  • Industrial Property Rights Holder: 国立大学法人名古屋大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-10-03
  • Overseas