Multidimensional approaches to molecular basis of schizophrenia

2009 Fiscal Year Final Research Report

• Project/Area Number: 18209012
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: Kyushu University
• Principal Investigator: FUKUMAKI Yasuyuki Kyushu University, 生体防御医学研究所, 教授 (90128083)
• Co-Investigator(Kenkyū-buntansha): IWAKI Akiko 九州大学, 生体防御医学研究所, 助教 (30253454)
• Project Period (FY): 2006 – 2009
• Keywords: 多因子病 / 統合失調症 / ゲノム / 関連解析 / 多型 / グルタミン酸 / 遺伝子改変マウス / 行動解析

Research Abstract

Schizophrenia is a devastating neuropsychiatric disorder with a multifactorial background. To search for susceptibility genes for schizophrenia, we have been taking four types of approaches, i) candidate gene, ii) PCP-responsive gene, iii) genome-wide and iv) model mouse approaches. We observed associations of GRM7, SLC1A6, SLC6A5, PDE4A, PLAT and C2orf24 with schizophrenia in approaches i, ii and iii. Comprehensive behavioral analyses, in approach iv, of mouse lines with targeted disruption of homologs of either GRIA4 or GRM3 with which we had previously reported associations of schizophrenia, revealed that GluR4^<-/-> mice showed impaired prepulse inhibition (PPI) and increased response to MK-801 in the open field test, and mGluR3^<-/-> mice exhibited hyperactivity in the open field and light/dark transition tests and impaired working memory in the T-maze test, suggesting involvement of these genes in generating schizophrenia endophenotypes.

Research Products

• [Journal Article] Association study of polymorphisms in the group III metabotropic glutamate receptor genes, GRM4 and GRM7, with schizophrenia. (2009)
  • Author(s): Shibata, H., Tani, A., Chikuhara, T., Kikuta, R., Sakai, M., Ninomiya, H., Tashiro, N., Iwata, N., Ozaki, N., Fukumaki, Y.
  • Journal Title: Psychiatry Res 167 Pages: 88-96
  • Peer Reviewed
• [Journal Article] The identification and functional implications of human-specific "fixed" amino acid substitutions in the glutamate receptor family. (2009)
  • Author(s): Goto, H., Watanabe, K., Araragi, N., Kageyama, R., Tanaka, K., Kuroki, Y., Toyoda, A., Hattori, M., Sakaki, Y., Fujiyama, A., Fukumaki, Y., Shibata, H.
  • Journal Title: BMC Evolutionary Biol 9 Pages: 224
  • Peer Reviewed
• [Journal Article] Association analysis of the glutamic acid decarboxylase 2 and the glutamine synthetase genes (GAD2, GLUL) with schizophrenia. (2009)
  • Author(s): Arai, K., Shibata, H., Sakai, M., Ninomiya, H., Iwata, N., Ozaki, N., Fukumaki, Y.
  • Journal Title: Psychiatr. Genet 19 Pages: 6-13
  • Peer Reviewed
• [Journal Article] Reversal of the expression pattern of Aldolase C mRNA in Purkinje cells and Ube 1x mRNA in Golgi cells by a dopamine D1 receptor agonist injections in the methamphetamine sensitized-rat cerebellum. (2008)
  • Author(s): Hamamura, M., Hirata, N., Sawada, K., Shuto, T., Shimazoe, T., Terada, Y., Fukumaki, Y.
  • Journal Title: J. Neural Transm 115 Pages: 959-971
  • Peer Reviewed
• [Journal Article] Association study of polymorphisms in the neutral amino acid transporter genes SLC1A4, SLC1A5 and the glycine transporter genes SLC6A5, SLC6A9 with schizophrenia. (2008)
  • Author(s): Deng, X., Sagata, N., Takeuchi, N, Tanaka, M., Takeuchi, N., Rachi, N., Ninomiya, H., Iwata, N., Ozaki, O., Shibata, H., Fukumaki, Y.
  • Journal Title: BMC Psychiatry 8 Pages: 58
  • Peer Reviewed
• [Journal Article] Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3 and SLC1A6 with schizophrenia. (2007)
  • Author(s): Deng, X., Shibata, H., Takeuchi, N., Rachi, N., Sakai, M., Ninomiya, H., Iwata, N., Ozaki, O., Fukumaki, Y.
  • Journal Title: Am. J. Med. Genet. Part B 144B Pages: 271-278
  • Peer Reviewed
• [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., Aramaki, T., Sakai, M., Ninomiya, H., Tashiro, N., Iwata, N., Ozaki, N., Fukumaki, Y.
  • Journal Title: Psychiatry Res 141 Pages: 39-51
  • Peer Reviewed
• [Presentation] Molecular evolutionary study of the ionotropic glutamate-receptor gene family as schizophrenia susceptibility genes: human-specific balancing selection in GRIN2B upstream region. (2009)
  • Author(s): Shibata, H., Tanaka, K., Watanabe, K., Goto, H., S. Mano, S., Takenaka, O., Fukumaki, Y.
  • Organizer: The 8th International Workshop on Advanced Genomics: Expansion of Genome Science
  • Place of Presentation: Tokyo
  • Year and Date: 20090617-20090618
• [Presentation] Genome-wide association study of schizophrenia using STR markers. (2009)
  • Author(s): Fukumaki, Y., Yamamoto, K., Sun, Z., Oka, A., Inoko, H., Arinami, T., Iwata, N., Ozaki, N., Shibata, H.
  • Organizer: The 59th Annual Meeting of The American Society of Human Genetics
  • Place of Presentation: Honolulu, HI, USA
  • Year and Date: 2009-10-22
• [Presentation] Molecular evolutionary study of the ionotropic glutamate-receptor gene family as schizophrenia susceptibility genes: human-specific balancing selection in the GRIN2B upstream region. (2009)
  • Author(s): Shibata, H., Watanabe, K., Tanaka, K., Goto, H., Mano, S., Takenaka, O., Fukumaki, Y.
  • Organizer: The 59th Annual Meeting of The American Society of Human Genetics
  • Place of Presentation: Honolulu, HI, USA
  • Year and Date: 2009-10-21
• [Presentation] Association study of phencyclidine-responsive genes with schizophrenia. (2008)
  • Author(s): Deng, X., Shibata, H., Kuroki, T., Nakahara, T., Hashimoto, K., Ninomiya, H., Iwata, N., Ozaki, N., Fukumaki, Y.
  • Organizer: 58th Annual Meeting of The American Society of Human Genetics
  • Place of Presentation: Philadelphia, PA
  • Year and Date: 2008-11-14
• [Presentation] Molecular evolutionary study of the ionotropic glutamate-receptor gene family as schizophrenia susceptibility genes: human-specific non-neutral pattern observed in GRIN2B upstream region. (2008)
  • Author(s): Shibata, H., Tanaka, K., Watanabe, K., Goto, H., Mano, S., Takenaka, O., Fukumaki, Y.
  • Organizer: XVIth World Congress on Psychiatric Genetics
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2008-10-15
• [Presentation] Search for schizophrenia susceptibility loci focusing on PCP-responsive genes as candidates. (2008)
  • Author(s): Fukumaki, Y., Deng, X., Kuroki, T., Nakahara, T., Hashimoto, K., Ninomiya, H., Iwata, N., Ozaki, N., Shibata, H.
  • Organizer: XVIth World Congress on Psychiatric Genetics
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2008-10-14
• [Presentation] Molecular evolutionary study of the ionotropic glutamate-receptor gene family as schizophrenia susceptibility genes: human-specific non-neutral pattern observed in GRIN2B upstream region. (2008)
  • Author(s): Shibata, H., Tanaka, K., Watanabe, K., Goto, H., Mano, S., Takenaka, O., Fukumaki, Y.
  • Organizer: XX International Congress of Genetics
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-07-16
• [Presentation] Genomic and animal model approaches to schizophrenia susceptibility. (2008)
  • Author(s): Fukumaki, Y.
  • Organizer: Joint 7th Human Genome Organization (HUGO)-Pacific Meeting and The 8th Asia-Pacific Conference on Human Genetics, Cebu
  • Place of Presentation: Philippines
  • Year and Date: 2008-04-02
• [Presentation] Molecular evolutionary study of the ionotropic glutamate-receptor gene family as schizophrenia susceptibility genes: human-specific non-neutral pattern observed in GRIN2B upstream region. (2007)
  • Author(s): Shibata, H., Tanaka, K., Watanabe, K., Goto, H., Takenaka, O., Fukumaki, Y.
  • Organizer: 57th Annual Meeting of The American Society of Human Genetics
  • Place of Presentation: San Diego, CA
  • Year and Date: 2007-10-24
• [Presentation] Association study of polymorphisms in the neutral amino acid transporter genes SLC1A4, SLC1A5 and the glycine transporter genes SLC6A9, SLC6A5 with schizophrenia. (2007)
  • Author(s): Deng, X., Sagata, N., Takeuchi, N., Tanaka, M., Shibata, H., Ninomiya, H., Iwata, N., Ozaki, N., Fukumaki Y.
  • Organizer: The XVth World Congress of Psychiatric Genetics
  • Place of Presentation: New York, NY
  • Year and Date: 2007-10-10
• [Presentation] Locus-wide association study of genes in the 5q33. 1 region with schizophrenia. (2006)
  • Author(s): Fukumaki, Y., Goto, H., Shibata, H., Takaji, M., Ninomiya, N., Tashiro N., Jarusuraisin, N.
  • Organizer: The XIVth World Congress of Psychiatric Genetics
  • Place of Presentation: Cagliari, Italy
  • Year and Date: 2006-10-30
• [Presentation] Locus-wide association study of 43 genes in the 5q33. 1 region with schizophrenia. (2006)
  • Author(s): Shibata, H., Goto, H., Takaji, M., Ninomiya, H., Tashiro, N., Jarusuraisin, N., Fukumaki Y.
  • Organizer: The 8th International Meeting on Human Genome Variation and Complex Genome Analysis
  • Place of Presentation: Hong Kong, China
  • Year and Date: 2006-09-14
• [Presentation] Locus-wide association study of schizophrenia with 43 genes located in the 5q33. 1 region. (2006)
  • Author(s): Shibata, H., Goto, H., Takaji, M., Ninomiya, H., Tashiro, N., Jarusuraisin, N., Fukumaki, Y.
  • Organizer: 11th International Congress of Human Genetics
  • Place of Presentation: Brisbane, Australia
  • Year and Date: 2006-08-09
• [Presentation] Association study of polymorphisms in the glutamate transporter genes, SLC1A1, SLC1A3, SLC1A6 and the neutral amino acid transporter genes SLC1A4, SLC1A5 with schizophrenia. (2006)
  • Author(s): Deng, X., Takeuchi, N., Shibata, H., Rachi, S., Sakai, M., Ninomiya, H., Iwata, N., Ozaki, N., Fukumaki, Y.
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2006-06-21
• [Book] 遺伝性疾患の概念と分子機構.分子病態学(一瀬白帝、鈴木宏治編) (2008)
  • Author(s): 服巻保幸
  • Total Pages: 97-106
  • Publisher: 中外医学社
• [Book] こころの病気に関わる遺伝子を求めて. ゲノムは何をどのように決めているのだろうか?-生命システムの理解に向けて(小原雄治編) (2007)
  • Author(s): 服巻保幸
  • Total Pages: 126-138
  • Publisher: クバプロ
• [Book] 統合失調症関連遺伝子. ゲノム医科学NOW(ゲノム4領域編) (2006)
  • Author(s): 服巻保幸
  • Total Pages: 195-211
  • Publisher: クバプロ
• [Remarks] 文部科学省科学研究費特定領域研究ゲノム4領域主催「ゲノムひろば」(平成20年10月25日,26日名古屋、平成18年11月18日, 19日京都)、および「ミニゲノムひろば」(平成21年12月20日福岡、平成20年12月21日福岡、平成19年12月23日福岡、平成18年12月10日福岡)に参加し学生や市民を対象に講演や出展を行った,福岡県立城南高等学校において出張講
• [Remarks]
  • URL: http://www.gen.kyushu-u.ac.jp/~byouin/