Functional analysis of schizoprenia risk gene, Neurogranin (NRGN)

• Project/Area Number: 24591680
• 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: YASUDA Yuka 大阪大学, 医学部附属病院, 特任助教 (20448062)
• Co-Investigator(Kenkyū-buntansha): YAMAMORI Hidenaga 大阪大学, 医学系研究科, 助教 (90570250) ; UMEDA Satomi 大阪大学, 医学系研究科, 研究員 (00625329)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 統合失調症 / ニューログラニン / 遺伝子解析 / 死後脳 / 認知機能 / 知能 / 脳構造画像 / NRGN遺伝子 / GWAS / ゲノム / 神経科学 / 遺伝子発現 / 前部帯状回灰白質体積 / IQ / 遺伝子 / 生物学的精神医学

Outline of Final Research Achievements

Genome-wide association studies (GWAS) have reported an association between schizophrenia and rs12807809 of the neurogranin (NRGN) gene. We have found that an rs12807809-rs12278912 haplotype of the gene is associated with schizophrenia in a Japanese population. The intellectual abilities of the high-risk TG/TG diplotype of the neurogranin gene were lower compared to those with the non-risk TA/TA diplotype. Our findings also suggested that the genome-wide associated genetic risk variant in the NRGN gene may be related to a small gray matter volume in the left anterior cingulate cortex in patients with schizophrenia. The lack of linkage between the risk gene polymorphisms and the expression levels of their major transcripts suggests that the control of pan mRNA levels may not be a prominent mechanism by which the genes identified in the GWAS contribute to the pathophysiology of schizophrenia.

Research Products

• [Journal Article] 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.
  • Journal Title: Schizophr Bull. Volume: 41 Issue: 4 Pages: 909-18
  • DOI: 10.1093/schbul/sbu171
  • NAID: 40020682401
  • 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: Schizophr Res. Volume: 160 Pages: 228-9
  • Peer Reviewed
• [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: 93-98
  • Peer Reviewed
• [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: 23-26
  • 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, Hashimoto R, Yamamori H, Weickert CS, Yasuda Y, Ohi K, Fujimoto M, Ito A, Takeda M.
  • Journal Title: Neurosci Lett. Volume: 568 Pages: 12-16
  • Peer Reviewed
• [Journal Article] A functional polymorphism of the GTP cyclohydrolase 1 gene predicts attention performance. (2014)
  • Author(s): Yasuda Y, Hashimoto R, Ohi K, Yamamori H, Fujimoto M, Umeda-Yano S, Fujino H, Fukunaga M, Horiguchi M, Takeda M, Ichinose H.
  • Journal Title: Neurosci Lett. Volume: 566 Pages: 46-49
  • Peer Reviewed
• [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: 68 Pages: 534-541
  • 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] 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] 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] A functional polymorphism of the GTP cyclohydrolase I gene predicts attention performance (2014)
  • Author(s): Yasuda Y, Hashimoto R, Ohi K, Yamamori H, Fujimoto M, Umeda-Yano S, Fujino H, Horiguchi M, Takeda M, Ichinose H
  • Journal Title: Neurosci Lett Volume: 566 Pages: 46-49
  • DOI: 10.1016/j.neulet.2014.02.019
  • 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] 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] The regulation of gene expression involved in TGF-β signaling by ZNF804A, a risk gene for schizophrenia. (2013)
  • Author(s): Umeda-Yano S, et al
  • Journal Title: Schizophr Res, Volume: e-pub
  • 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
• [Journal Article] Analysis of the VAV3 as candidate gene for schizophrenia: evidences from voxel based morphometry and mutation screening. (2012)
  • Author(s): Aleksic B., et al ,
  • Journal Title: Schizophrenia Bulletin. Volume: e-pub
  • Peer Reviewed
• [Journal Article] Expression analysis of a novel mRNA variant of the schizophrenia risk gene ZNF804A. (2012)
  • Author(s): Okada T, et al,
  • Journal Title: Schizophr Res, Volume: 141(2-3): Issue: 2-3 Pages: 277-278
  • DOI: 10.1016/j.schres.2012.08.015
  • 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] Personality traits and schizophrenia : evidence from a case-control study and meta-analysis (2012)
  • Author(s): Ohi K, Hashimoto R, Yasuda Y, Fukumoto M, Yamamori H, Iwase M, Kazui H, Takeda M
  • Journal Title: Psychiatry Res Volume: (Epub ahead of print) Issue: 1 Pages: 7-11
  • DOI: 10.1016/j.psychres.2011.12.018
  • 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] 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] The p250GAP gene is associated with risk for schizophrenia and schizotypal personality traits (2012)
  • Author(s): Hashimoto R
  • Journal Title: PLoS ONE Volume: 7 Issue: 4 Pages: e35696-e35696
  • DOI: 10.1371/journal.pone.0035696
  • URL: https://pure.teikyo.jp/en/publications/4db5e609-1ad4-45ab-8119-8a26d97d88c8
  • Peer Reviewed
• [Journal Article] The AKT1 gene is associated with attention and brain morphology in schizophrenia (2011)
  • Author(s): Ohi K, Hashimoto R, et al
  • Journal Title: World J Biol Psychiatry Volume: e-pub Issue: 2 Pages: 100-13
  • DOI: 10.3109/15622975.2011.591826
  • Peer Reviewed
• [Journal Article] The KCNH2 gene is associated with neurocognition and the risk of schizophrenia (2011)
  • Author(s): Hashimoto R, et al
  • Journal Title: World J Biol Psychiatry. Volume: e-pub Issue: 2 Pages: 114-20
  • DOI: 10.3109/15622975.2011.604350
  • Peer Reviewed
• [Presentation] 統合失調症のGWASによるプレパルス抑制との共通リスク遺伝子の同定 (2014)
  • Author(s): 近藤健治、橋本亮太、池田匡志、高橋秀俊、山森英長、岸太郎、安田由華、島崎愛夕、藤本美智子、大井一高、斉藤竹生、武田雅俊、岩田仲生
  • Organizer: 第47回精神神経系薬物治療研究報告会、大阪、12.5, 2014. ポスター
  • Place of Presentation: 大阪、日本
  • Year and Date: 2014-12-05
• [Presentation] 統合失調症患者の静止画自由視時の視線データはサリエンシー計算論モデルによって説明できる (2014)
  • Author(s): 吉田正俊、三浦健一郎、橋本亮太、藤本美智子、山森英長、安田由華、大井一高、武田雅俊、伊佐正
  • Organizer: 第4回生理研-名大合同シンポジウム
  • Place of Presentation: 名古屋、日本
  • Year and Date: 2014-11-22
• [Presentation] Genome-wide association study of cognitive decline in schizophrenia (統合失調症の認知機能障害の全ゲノム関連解析) (2014)
  • Author(s): 橋本亮太、池田匡志、大井一高、安田由華、山森英長、福本素由己、梅田知美、Dickinson D、Aleksic B.、岩瀬真生、数井裕光、尾崎紀夫、Weinberger DR、岩田仲生、武田雅俊
  • Organizer: 第59回日本人類遺伝学会 第21回日本遺伝子診療学会合同大会
  • Place of Presentation: 東京、日本
  • Year and Date: 2014-11-19 – 2014-11-22
• [Presentation] 統合失調症患者の認知機能障害の簡易測定法の開発 (2014)
  • Author(s): 橋本亮太、住吉チカ、藤野陽生、山森英長、藤本美智子、安田由華、大井一高、井村修、住吉太幹、武田雅俊
  • Organizer: 第14回精神疾患と認知機能研究会
  • Place of Presentation: 東京、日本
  • Year and Date: 2014-11-08
  • Invited
• [Presentation] 統合失調症患者の社会機能に影響する要因 (2014)
  • Author(s): 藤野陽生、橋本亮太、住吉チカ、住吉太幹、山森英長、藤本美智子、安田由華、大井一高、武田雅俊、井村修
  • Organizer: 第14回精神疾患と認知機能研究会
  • Place of Presentation: 東京、日本
  • Year and Date: 2014-11-08
• [Presentation] 統合失調症患者由来サンプルを用いた統合失調症の病態解明研究 (2014)
  • Author(s): 橋本亮太、山森英長、梅田知美、藤本美智子、安田由華、伊藤彰、武田雅俊
  • Organizer: 第11回NDDC-JSG会議
  • Place of Presentation: 大阪、日本
  • Year and Date: 2014-10-07
• [Presentation] 我が国の発達障害研究はトランスレーショナルとなりうるか？ (2014)
  • Author(s): 橋本亮太、安田由華、山森英長、大井一高、藤本美智子、梅田知美、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、日本
  • Year and Date: 2014-09-29 – 2014-10-01
  • Invited
• [Presentation] 「多施設共同研究の意義と日本における現状：欧米に勝つための戦略とは？」 (2014)
  • Author(s): 橋本亮太、大井一高、山森英長、安田由華、藤本美智子、梅田知美、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、日本
  • Year and Date: 2014-09-29 – 2014-10-01
  • Invited
• [Presentation] プレパルス抑制関連遺伝子の探索 (2014)
  • Author(s): 近藤健治、橋本亮太、池田匡志、高橋秀俊、山森英長、岸太郎、安田由華、島崎愛夕、藤本美智子、大井一高、斉藤竹生、武田雅俊、岩田仲生
  • 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、日本
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] 統合失調症の生物学的マーカーとしての眼球運動スコアの開発、An integrated eye movement score for biological marker of schizophrenia (2014)
  • Author(s): 藤本美智子、橋本亮太、三浦健一郎、山森英長、安田由華、大井一高、梅田知美、岩瀬真生、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、日本
  • Year and Date: 2014-09-29 – 2014-10-01
• [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（Assessment of a multi-assay biological diagnostic test for mood disorders and schizophrenia） (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、日本
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] 治療抵抗性統合失調症への果てしなき挑戦：治療のゴールはどこにあるのか？ (2014)
  • Author(s): 橋本亮太、山森英長、藤本美智子、安田由華、大井一高、梅田知美、武田雅俊
  • Organizer: 第110回日本精神神経学会学術総会
  • Place of Presentation: 横浜、日本
  • Year and Date: 2014-06-26 – 2014-06-28
• [Presentation] 孤発性自閉症スペクトラム障害のトリオにおけるエクソーム解析によるde novo変異の同定、 (2014)
  • Author(s): 安田由華、
  • Organizer: 新学術領域研究「脳疾患のゲノム情報」第二回研究班会議、
  • Place of Presentation: 東京
• [Presentation] Impaired cognitive flexibility in Japanese patients with Autism Spectrum Disorders in the Wisconsin Card Sorting Test. (2013)
  • Author(s): Yasuda Y,
  • Organizer: 11th World Congress of Biological Psychiatry,
  • Place of Presentation: 京都
• [Presentation] 自閉症スペクトラム障害を合併した統合失調症のパーソナルゲノム解析、 (2013)
  • Author(s): 安田由華、
  • Organizer: 新学術領域研究「脳疾患のゲノム情報」第一回研究班会議、
  • Place of Presentation: 東京
• [Presentation] 日本人の成人自閉症スペクトラム障害患者におけるWCSTを用いた認知の柔軟性の障害の検討、 (2013)
  • Author(s): 安田由華
  • Organizer: Neuro 2013
  • Place of Presentation: 京都
• [Presentation] 自閉症スペクトラム障害におけるハノイの塔課題時の前頭葉の血流低下について：２チャンネルNIRS（Near Infra- Red Spectroscopy）による脳機能計測研究、 (2012)
  • Author(s): 安田由華
  • Organizer: 第22回日本臨床精神神経薬理学会第42回日本神経精神薬理学会合同年会
  • Place of Presentation: 栃木
• [Presentation] 自閉症スペクトラム障害におけるハノイの塔課題時の前頭葉の血流低下：2チャンネルNIRSによる研究-Reduced prefrontal activation in Autism Spectrum Disorders:A two-channel NIRS study- (2012)
  • Author(s): 安田由華
  • Organizer: 第34回日本生物学的精神医学会
  • Place of Presentation: 神戸
• [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] 今後期待される新しいメカニズムの向精神薬、臨床精神薬理 (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: 星和書店
• [Book] 統合失調症入院プログラムにおける治療抵抗性統合失調症に対するclozapineの有用性 (2012)
  • Author(s): 橋本亮太
  • Publisher: 臨床精神薬理、星和書店
• [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