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Searching for susceptibility genes in narcolepsy, and the therapeutic application

Research Project

Project/Area Number 23689022
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Human genetics
Research InstitutionThe University of Tokyo

Principal Investigator

MIYAGAWA TAKU  東京大学, 医学(系)研究科(研究院), 助教 (20512263)

Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥27,430,000 (Direct Cost: ¥21,100,000、Indirect Cost: ¥6,330,000)
Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2013: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2012: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2011: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Keywordsゲノム / 遺伝学 / ゲノムワイド関連解析 / ナルコレプシー / 睡眠障害 / カルニチン / HLA / CNV / 脂肪酸代謝 / Copy number variation
Outline of Final Research Achievements

I performed association studies to identify novel genetic factors for narcolepsy. HLA-DQB1*03:02, HLA-DPB1*05:01 and low frequency CNVs in PARK2 gene region were found to be associated with narcolepsy. In addition, I found a significant association between essential hypersomnia and a SNP in CRAT gene region.
To assess the efficacy of oral l-carnitine for the treatment of narcolepsy, I performed a clinical trial administering L-carnitine (510 mg/day) to patients with narcolepsy. L-carnitine treatment significantly improved the total time for dozing off during the daytime compared with that of placebo-treated periods. This study suggests that oral L-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (37 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Acknowledgement Compliant: 2 results,  Open Access: 2 results) Presentation (19 results) (of which Invited: 3 results) Book (4 results) Remarks (4 results)

  • [Journal Article] New susceptibility variants to narcolepsy identified in HLA class II region.2015

    • Author(s)
      Miyagawa T, Toyoda H, Hirataka A, Kanbayashi T, Imanishi A, Honda M, Tokunaga K, et al.
    • Journal Title

      Hum. Mol. Genet.

      Volume: 24 Issue: 3 Pages: 891-898

    • DOI

      10.1093/hmg/ddu480

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Immune-related pathways including HLA-DRB1(*)13:02 are associated with panic disorder.2015

    • Author(s)
      Shimada-Sugimoto M ほか
    • Journal Title

      Brain Behav Immun

      Volume: Epub Pages: 96-103

    • DOI

      10.1016/j.bbi.2015.01.002

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-accuracy imputation for HLA class I and II genes based on high-resolution SNP data of population-specific references.2015

    • Author(s)
      Khor SS, Yang W, Kawashima M, Kamitsuji S, Zheng X, Nishida N, Sawai H, Toyoda H, Miyagawa T, Honda M, Kamatani N, Tokunaga K.
    • Journal Title

      Pharmacogenomics J.

      Volume: 未定 Issue: 6 Pages: 1-8

    • DOI

      10.1038/tpj.2015.4

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Genetic overlap between antipsychotic response and susceptibility to schizophrenia2015

    • Author(s)
      Ikeda M, Yoshimura R, Hashimoto R, Kondo K, Saito T, Shimasaki A, Ohi K, Tochigi M, Kawamura Y, Nishida N, Miyagawa T, Sasaki T, Tokunaga K, Kasai K, Takeda M, Nakamura J, Ozaki N, Iwata N.
    • Journal Title

      Journal of Clinical Psychopharmacology

      Volume: 35(1) Issue: 1 Pages: 85-88

    • DOI

      10.1097/jcp.0000000000000268

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide analysis of CNV (copy number variation) and their associations with narcolepsy in a Japanese population2014

    • Author(s)
      Yamasaki M, Miyagawa T, Toyoda H, Khor SS, Koike A, Nitta A, Akiyama K, Sasaki T, Honda M, and Tokunaga K
    • Journal Title

      J. Hum. Genet.

      Volume: 印刷中 Issue: 5 Pages: 235-240

    • DOI

      10.1038/jhg.2014.13

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide association study of atypical psychosis2013

    • Author(s)
      金沢 徹文 他
    • Journal Title

      American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

      Volume: 162 Issue: 7 Pages: 679-686

    • DOI

      10.1002/ajmg.b.32164

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evidence for shared genetic risk between methamphetamine-induced psychosis and schizophrenia2013

    • Author(s)
      池田 匡志 他
    • Journal Title

      Neuropsychopharmacology

      Volume: 38 Issue: 10 Pages: 1864-1870

    • DOI

      10.1038/npp.2013.94

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of oral L-carnitine administration in narcolepsy patients: a randomized, double-blind, cross-over and placebo-controlled trial2013

    • Author(s)
      宮川 卓 他
    • Journal Title

      PLoS One

      Volume: 8(1) Issue: 1 Pages: e53707-e53707

    • DOI

      10.1371/journal.pone.0053707

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide association study of HLA-DQB1*06:02 negative essential hypersomnia2013

    • Author(s)
      Seik-Soon Khor 他
    • Journal Title

      PeerJ

      Volume: 掲載確定

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meta-analysis of genome-wide association studies for panic disorder in Japanese population.2012

    • Author(s)
      Otowa T 1/32, Umekage T 17/32, Sasaki T 32/32
    • Journal Title

      Translational Psychiatry

      Volume: 13;2 Issue: 11 Pages: 1-8

    • DOI

      10.1038/tp.2012.89

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] ナルコレプシーとHLA-DQB1*06:01 およびDQB1*03:02 との関連2014

    • Author(s)
      宮川 卓 他
    • Organizer
      日本人類遺伝学会第59回大会・日本遺伝子診療学会第21回大会  合同大会
    • Place of Presentation
      タワーホール船堀(江戸川区)
    • Year and Date
      2014-11-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Association analysis of HLA-DQB1 gene with narcolepsy without cataplexy and idiopathic hypersomnia2014

    • Author(s)
      宮川 卓 他
    • Organizer
      The American Society of Human Genetics Annual Meeting
    • Place of Presentation
      San Diego Convention Center(サンディエゴ、アメリカ)
    • Year and Date
      2014-10-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 情動脱力発作を伴わないナルコレプシーとHLA-DQB1との関連2014

    • Author(s)
      宮川 卓 他
    • Organizer
      第23回日本組織適合性学会
    • Place of Presentation
      長崎大学(長崎市)
    • Year and Date
      2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] ナルコレプシーの感受性遺伝子の探索2014

    • Author(s)
      宮川 卓 他
    • Organizer
      日本睡眠学会第39回定期学術集会
    • Place of Presentation
      あわぎんホール(徳島市)
    • Year and Date
      2014-07-03
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ナルコレプシーの感受性遺伝子の探索2013

    • Author(s)
      宮川 卓
    • Organizer
      日本睡眠学会第38回定期学術集会
    • Place of Presentation
      秋田キャッスルホテル(秋田市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ナルコレプシーの感受性遺伝子の探索及び治療への応用2013

    • Author(s)
      宮川 卓
    • Organizer
      日本人類遺伝学会第58回大会
    • Place of Presentation
      江陽グランドホテル(仙台市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Decreased long chain acylcarnitines in narcolepsy2013

    • Author(s)
      本多 真 他
    • Organizer
      第27回アメリカ睡眠学会(27th Annual Meeting of the Associated Professional Sleep Societies)
    • Place of Presentation
      Baltimore Convention Center(ボルティモア、アメリカ)
    • Related Report
      2013 Annual Research Report
  • [Presentation] ゲノムワイド関連解析によるナルコレプシー疾患感受性遺伝子の探索2013

    • Author(s)
      豊田 裕美 他
    • Organizer
      日本人類遺伝学会第58回大会
    • Place of Presentation
      江陽グランドホテル(仙台市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 内臓脂肪蓄積に関与するTRIB2遺伝子多型とナルコレプシーの関連解析研究2013

    • Author(s)
      中山 歩美 他
    • Organizer
      日本人類遺伝学会第58回大会
    • Place of Presentation
      江陽グランドホテル(仙台市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] ナルコレプシーとHLA-DQB1*06:01 およびDQB1*03:02 との関連2013

    • Author(s)
      宮川 卓 他
    • Organizer
      第22回日本組織適合性学会
    • Place of Presentation
      コラッセふくしま(福島市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] HLA-DQB1*03:02 is associated with narcolepsy-cataplexy in the Japanese population2013

    • Author(s)
      宮川 卓 他
    • Organizer
      アメリカ人類遺伝学会2013年(The American Society of Human Genetics Annual Meeting2013)
    • Place of Presentation
      Boston Convention & Exhibition Center(ボストン、アメリカ)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Genome-wide copy number variation analysis of narcolepsy in the Japanese population2013

    • Author(s)
      山崎 茉莉亜 他
    • Organizer
      第27回アメリカ睡眠学会(27th Annual Meeting of the Associated Professional Sleep Societies)
    • Place of Presentation
      Baltimore Convention Center(ボルティモア、アメリカ)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Common variants in NCKAP5, SPRED1, and CRAT are associated with susceptibility to HLA DQB1*06:02 negative essential hypersomnia2013

    • Author(s)
      Khor Seik Soon 他
    • Organizer
      日本睡眠学会第 38 回定期学術集会
    • Place of Presentation
      秋田キャッスルホテル(秋田市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 日本人ナルコレプシー患者におけるゲノムワイドCNV(Copy Number Variation)解析2013

    • Author(s)
      山崎 茉莉亜 他
    • Organizer
      日本睡眠学会第 38 回定期学術集会
    • Place of Presentation
      秋田キャッスルホテル(秋田市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Genome-wide association study of HLA-DQB1*06:02 negative essential hypersomnia2013

    • Author(s)
      Khor Seik Soon 他
    • Organizer
      アメリカ人類遺伝学会2013年(The American Society of Human Genetics Annual Meeting2013)
    • Place of Presentation
      Boston Convention & Exhibition Center(ボストン、アメリカ)
    • Related Report
      2012 Annual Research Report
  • [Presentation] ナルコレプシーの疾患感受性遺伝子の探索及び治療への応用2012

    • Author(s)
      宮川 卓、 徳永 勝士
    • Organizer
      日本睡眠学会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] L-カルニチンのナルコレプシーに対する臨床評価2012

    • Author(s)
      宮川 卓 他
    • Organizer
      日本組織適合性学会
    • Place of Presentation
      明治大学(東京都千代田区)
    • Related Report
      2011 Annual Research Report
  • [Presentation] L-カルニチンのナルコレプシー患者に対する臨床評価2012

    • Author(s)
      宮川 卓 他
    • Organizer
      日本人類遺伝学会
    • Place of Presentation
      京王プラザホテル (東京都新宿区)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Effects of oral l-carnitine administration in narcolepsy patients2012

    • Author(s)
      宮川 卓 他
    • Organizer
      The American Society of Human Genetics Annual Meeting
    • Place of Presentation
      Moscone Center(アメリカ サンフランシスコ)
    • Related Report
      2011 Annual Research Report
  • [Book] こどもの病気 遺伝について聞かれたら (ナルコレプシー)2015

    • Author(s)
      宮川 卓
    • Total Pages
      2
    • Publisher
      診断と治療社
    • Related Report
      2014 Annual Research Report
  • [Book] 産婦人科の実際(遺伝疫学-多因子疾患感受性遺伝子の探索法-)2015

    • Author(s)
      宮川 卓、徳永 勝士
    • Total Pages
      5
    • Publisher
      金原出版株式会社
    • Related Report
      2014 Annual Research Report
  • [Book] ナルコレプシー感受性および薬剤副作用とHLA2013

    • Author(s)
      宮川 卓、徳永 勝士
    • Total Pages
      5
    • Publisher
      医薬ジャーナル社
    • Related Report
      2012 Annual Research Report
  • [Book] 医学のあゆみ ナルコレプシーと脂肪酸代謝2011

    • Author(s)
      宮川 卓
    • Total Pages
      2
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2011 Annual Research Report
  • [Remarks] 東京大学大学院医学系研究科国際保健学専攻人類遺伝学分野

    • URL

      http://www.humgenet.m.u-tokyo.ac.jp/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京大学大学院医学系研究科人類遺伝学教室

    • URL

      http://www.humgenet.m.u-tokyo.ac.jp/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 東京大学大学院医学系研究科人類遺伝学教室

    • URL

      http://www.humgenet.m.u-tokyo.ac.jp/

    • Related Report
      2012 Annual Research Report
  • [Remarks] http://www.humgenet.m.u-tokyo.ac.jp/

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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