Analysis of schizophrenia risk gene ZNF804A

• Project/Area Number: 25461730
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: YAMAMORI HIDENAGA 大阪大学, 医学(系)研究科(研究院), 助教 (90570250)
• Co-Investigator(Kenkyū-buntansha): YASUDA Yuka 大阪大学, 医学部附属病院, 特任助教 (20448062) ; UMEDA Tomomi 大阪大学, 医学系研究科, 特任研究員 (00625329)
• Co-Investigator(Renkei-kenkyūsha): HASHIMOTO Ryota 大阪大学, 大学院連合小児発達学研究科, 准教授 (10370983)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 統合失調症 / 全ゲノム関連解析 / ZNF804A遺伝子 / 中間表現型 / 死後脳 / リンパ芽球

Outline of Final Research Achievements

Genome-wide association studies (GWAS) and meta-analyses have highlighted ZNF804A as a robust, genome wide supported susceptibility gene for schizophrenia; however, the biological functions of ZNF804A have not yet been fully elucidated. The aim of this study is to see the effect of ZNF804A gene on various phenotypes of brain, like neurocognition, neuroimaging, neurophysiology, personality trait and gene expressions. We also investigated the differential expression of this gene in schizophrenia. We identified a novel transcriptional variant of ZNF804A that contains an additional sequence and found that significantly fewer schizophrenic patients than controls expressed the variant in the lymphoblast. We also found that ZNF804A is involved in the TGF-β signaling. Expression levels of ZNF804A in the postmortem brain and the effect of risk genotype on expression levels were also investigated.

Research Products

• [Journal Article] Assessment of a multi-assay biological diagnostic test for mood disorders in a Japanesepopulation. (2015)
  • Author(s): Yamamori H, Ishima T, Yasuda Y, Fujimoto M, Kudo N, Ohi K, Hashimoto K, Takeda M, Hashimoto R.
  • Journal Title: Neurosci Lett Volume: 612 Pages: 167-171
  • DOI: 10.1016/j.neulet.2015.12.019
  • Peer Reviewed / Open Access
• [Journal Article] Expression analysis of the genes identified in GWAS of the postmortem brain tissues from patients with schizophrenia. (2014)
  • Author(s): Umeda-Yano S, et al.
  • Journal Title: Neuroscience Letters Volume: in press Pages: 12-6
  • DOI: 10.1016/j.neulet.2014.03.031
  • Peer Reviewed / Open Access
• [Journal Article] An integrated eye movement score as a neurophysiological marker of schizophrenia (2014)
  • Author(s): Miura K, Hashimoto R, Fujimoto M, Yamamori H, Yasuda Y, Ohi K, Umeda-Yano S, Fukunaga M, Iwase M, Takeda M
  • Journal Title: Schizophrenia Research Volume: 160(1-3) Issue: 1-3 Pages: 228-9
  • DOI: 10.1016/j.schres.2014.10.023
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Behavioral characterization of mice overexpressing human dysbindin-1 (2014)
  • Author(s): Shintani N, Onaka Y, Hashimoto R, Takamura H, Nagata T, Umeda-Yano S, Mouri A, Mamiya T, Haba R, Matsuzaki S, Katayama T, Yamamori H, Nakazawa T, Nagayasu K, Ago Y, Yagasaki Y, Nabeshima T, Takeda M, Hashimoto H
  • Journal Title: Molecular Brain Volume: 7(1) Issue: 1 Pages: 74-74
  • DOI: 10.1186/s13041-014-0074-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Common variants at 1p36 are associated with superior frontal gyrus volume. (2014)
  • Author(s): Hashimoto R, Ikeda M, Yamashita F, Ohi K, Yamamori H, Yasuda Y, Fujimoto M, Fukunaga M, Nemoto K, Takahashi T, Tochigi M, Onitsuka T, Yamasue H, Matsuo K, Iidaka T, Iwata N, Suzuki M, Takeda M, Kasai K, Ozaki N
  • Journal Title: Translational Psychiatry Volume: 4 Issue: 10 Pages: e472-e472
  • DOI: 10.1038/tp.2014.110
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Changes in plasma D-serine, L-serine, and glycine levels in treatment-resistant schizophrenia before and after clozapine treatment. (2014)
  • Author(s): Yamamori H, Hashimoto R, Fujita Y, Numata S, Yasuda Y, Fujimoto M, Ohi K, Umeda-Yano S, Ito A, Ohmori T, Hashimoto K, Takeda M.
  • Journal Title: Neurosci Lett. Volume: 582 Pages: 93-8
  • DOI: 10.1016/j.neulet.2014.08.052
  • Peer Reviewed
• [Journal Article] Duplication of the NPHP1 gene in patients with autism spectrum disorder and normal intellectual ability: a case series. (2014)
  • Author(s): Yasuda Y, Hashimoto R, Fukai R, Okamoto N, Hiraki Y, Yamamori H, Fujimoto M, Ohi K, Taniike M, Mohri I, Nakashima M, Tsurusaki Y, Saitsu H, Matsumoto N, Miyake N, Takeda M.
  • Journal Title: Ann Gen Psychiatry. Volume: 13 Issue: 1 Pages: 22-26
  • DOI: 10.1186/s12991-014-0022-2
  • Peer Reviewed / Open Access
• [Journal Article] Performance on the Wechsler Adult Intelligence Scale-III in Japanese patients with schizophrenia. (2014)
  • Author(s): Fujino H, Sumiyoshi C, Sumiyoshi T, Yasuda Y, Yamamori H, Ohi K, Fujimoto M, Umeda-Yano S, Higuchi A, Hibi Y, Matsuura Y, Hashimoto R, Takeda M, Imura O.
  • Journal Title: Psychiatry Clin Neurosci. Volume: in press Issue: 7 Pages: 534-541
  • DOI: 10.1111/pcn.12165
  • Peer Reviewed
• [Journal Article] Cognitive inflexibility in Japanese adolescents and adults with autism spectrum disorders. (2014)
  • Author(s): Yasuda Y, Hashimoto R, Ohi K, Yamamori H, Fujimoto M, Umeda-Yano S, Fujino H, Takeda M.
  • Journal Title: World J Psychiatry. Volume: 22 Issue: 2 Pages: 42-8
  • DOI: 10.5498/wjp.v4.i2.42
  • Peer Reviewed / Open Access
• [Journal Article] Genetic risk variants of schizophrenia associated with left superior temporal gyrus volume. (2014)
  • Author(s): Ohi K, Hashimoto R, Ikeda M, Yamashita F, Fukunaga M, Nemoto K, Ohnishi T, Yamamori H, Yasuda Y, Fujimoto M, Umeda-Yano S, Watanabe Y, Iwata N, Weinberger DR, Takeda M.
  • Journal Title: Cortex Volume: 58 Pages: 23-6
  • DOI: 10.1016/j.cortex.2014.05.011
  • Peer Reviewed / Open Access
• [Journal Article] Association between genetic polymorphism rs2952768, close to the METTL21A and CREB1 genes, and intellectual ability in healthy subjects. (2014)
  • Author(s): Nishizawa D, et al.
  • Journal Title: Journal of Addiction Research & Therapy Volume: in press
  • Peer Reviewed
• [Journal Article] Imaging genetics and psychiatric disorders. (2014)
  • Author(s): Hashimoto R, et al.
  • Journal Title: Current Molecular Medicine Volume: in press
  • Peer Reviewed
• [Journal Article] A functional polymorphism (C-824T) of the tyrosine hydroxylase gene affects intelligence quotient in schizophrenia (2014)
  • Author(s): Horiguchi M, Ohi K, Hashimoto R, Hao Q, Yasuda Y, Yamamori H, Fujimoto M, Umeda-Yano S, Takeda M, Ichinose H
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 68(6) Issue: 6 Pages: 456-62
  • DOI: 10.1111/pcn.12157
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Relation between remission status and attention in patients withn schizophrenia. (2014)
  • Author(s): Fukumoto M, et al.
  • Journal Title: Psychiatry and Clinical Neurosciences, Volume: 68(3) Issue: 3 Pages: 234-41
  • DOI: 10.1111/pcn.12119
  • Peer Reviewed
• [Journal Article] Deletion of SHATI/NAT8L increases dopamine D1 receptor on the cell surface in the nucleus accumbens, accelerating methamphetamine dependence (2014)
  • Author(s): Toriumi K, Kondo M, Nagai T, Hashimoto R, Ohi K, Song Z, Tanaka J, Mouri A, Koseki T, Yamamori H, Furukawa-Hibi Y, Mamiya T, Fukushima T, Takeda M, Nitta A, Yamada K, Nabeshima T
  • Journal Title: Int J Neuropsychopharmacol Volume: 17 Issue: 03 Pages: 443-453
  • DOI: 10.1017/s1461145713001302
  • Peer Reviewed / Open Access
• [Journal Article] Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine. (2013)
  • Author(s): Yamamori H, et al.
  • Journal Title: Neurosci Lett, Volume: 556( Pages: 37-41
  • DOI: 10.1016/j.neulet.2013.09.059
  • Peer Reviewed
• [Journal Article] Influence of the NRGN gene on intellectual ability in schizophrenia. (2013)
  • Author(s): Ohi K, et al.
  • Journal Title: Journal of Human Genetics, Volume: 58(10) Issue: 10 Pages: 700-5
  • DOI: 10.1038/jhg.2013.82
  • Peer Reviewed
• [Journal Article] The impact of the genome-wide supported variant in the cyclin M2 gene on gray matter morphology in schizophrenia. (2013)
  • Author(s): Ohi K, et al.
  • Journal Title: Behavioral and Brain Functions, Volume: 9(1) Issue: 1 Pages: 40-40
  • DOI: 10.1186/1744-9081-9-40
  • Peer Reviewed
• [Journal Article] How to diagnose the 22q11.2 deletion syndrome in patients with schizophrenia: a case report. (2013)
  • Author(s): Ohi K, et al.
  • Journal Title: Annals of General Psychiatry, Volume: 12(1) Issue: 1 Pages: 29-29
  • DOI: 10.1186/1744-859x-12-29
  • Peer Reviewed
• [Journal Article] Genome-wide association study of cognitive decline in schizophrenia. (2013)
  • Author(s): Hashimoto R, et al.
  • Journal Title: Am J Psychiatry Volume: 170(6) Issue: 6 Pages: 683-4
  • DOI: 10.1176/appi.ajp.2013.12091228
  • Peer Reviewed
• [Journal Article] Analysis of the VAV3 as candidate gene for schizophrenia : evidences from voxel based morphometry and mutation screening. (2012)
  • Author(s): Aleksic B, Kushima I, Hashimoto R, Ohi K, Ikeda M, Yoshimi A, Nakamura Y, Ito Y, Okochi T, Fukuo Y, Yasuda Y, Fukumoto M, Yamamori H, Ujike H, Suzuki M, Inada T, Takeda M, Kaibuchi K, Iwata N, Ozaki N
  • Journal Title: Schizophrenia Bulletin Volume: 39 Issue: 3 Pages: 39-39
  • DOI: 10.1093/schbul/sbs038
  • Peer Reviewed
• [Presentation] 複数のバイオマーカーを用いた統合失調症の補助診断方法確立の検討、 (2015)
  • Author(s): 山森英長、橋本亮太、石間環、藤本美智子、安田由華、大井一高、新津富央、沼田周助、大森哲郎、伊豫雅臣、橋本謙二、武田雅俊、
  • Organizer: 第10回統合失調症学会
  • Place of Presentation: 東京
  • Year and Date: 2015-03-27
• [Presentation] Glutamate Networks Implicate Cognitive Impairments in Schizophrenia; Genome-Wide Association Studies of 52 Cognitive Phenotypes. (2014)
  • Author(s): Ohi K, Hashimoto R, Ikeda M, Yamamori H, Yasuda Y, Fujimoto M, Umeda-Yano S, Fukunaga M, Fujino H, Watanabe Y, Iwase M, Kazui H, Iwata N, Weinberger DR, Takeda M.
  • Organizer: 2014 American College of Neuropharmachology(ACNP)
  • Place of Presentation: Phoenix, U.S.A.
  • Year and Date: 2014-12-09
• [Presentation] 複数のバイオマーカーを用いた気分障害と統合失調症の補助診断方法確立の検討 (2014)
  • Author(s): 山森英長、橋本亮太、石間環、藤本美智子、安田由華、大井一高、梅田知美、伊藤彰、橋本謙二、武田雅俊、
  • Organizer: 第36回日本生物学的精神医学会・第57回日本神経化学会大会合同年会
  • Place of Presentation: 奈良
  • Year and Date: 2014-10-01
• [Presentation] Intermediate phenotype studies in schizophrenia (2014)
  • Author(s): Hashimoto R, Ohi K, Yamamori H, Yasuda Y, Fujimoto M, Umeda-Yano S, Takeda M.
  • Organizer: 29th CINP World Congress of Neuropsychopharmacology
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2014-06-23
• [Presentation] Changes in plasma D-serine, and glycine levels in treatment-resistant schizophrenia before and after treatment with clozapine. (2014)
  • Author(s): Yamamori H,
  • Organizer: 第9回日本統合失調症学会、
  • Place of Presentation: 京都
• [Presentation] Expression analysis of the genes identified by GWAS in postmortem brain tissues from schizophrenia. (2013)
  • Author(s): Yamamori H,
  • Organizer: 11th World Congress of Biological Psychiatry,
  • Place of Presentation: 京都
• [Presentation] クロザピン治療を受けた治療抵抗性統合失調症患者血漿中のmature BDNFとMMP-9の濃度の検討 (2013)
  • Author(s): 山森英長、
  • Organizer: 第23回日本臨床精神神経薬理学会・第43回日本神経精神薬理学会合同年会、
  • Place of Presentation: 沖縄
• [Presentation] Expression analysis of the genes identified by GWAS in postmortem brain tissues from schizophrenia. (2013)
  • Author(s): Yamamori H,
  • Organizer: Neuro 2013
  • Place of Presentation: 京都
• [Book] 治療抵抗性統合失調症の治療戦略と病態研究-真の治療抵抗性統合失調症と見かけ上の治療抵抗性統合失調症、臨床精神薬理 (2014)
  • Author(s): 橋本亮太、安田由華、山森英長、藤本美智子、武田雅俊、
  • Publisher: 星和書店
• [Book] イメージングジェネティクスで精神疾患に迫る、Medical Scienece Digest (2014)
  • Author(s): 橋本亮太、山森英長、安田由華、大井一高、藤本美智子、梅田知美、武田雅俊、
  • Publisher: ニューサイエンス社
• [Remarks] 大阪大学大学院医学系研究科精神医学教室分子精神医学研究グループ
  • URL: http://www.sp-web.sakura.ne.jp/lab/index.html
• [Remarks] 分子精神医学研究グループ
  • URL: http://www.sp-web.sakura.ne.jp/lab/index.html
• [Remarks] 分子精神医学研究グループ
  • URL: http://www.sp-web.sakura.ne.jp/lab/index.html