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Genetic and environmental interactions that determine sleep and circadian deterioration with advancing age

Research Project

Project/Area Number 16H05381
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionAkita University (2018)
National Center of Neurology and Psychiatry (2016-2017)

Principal Investigator

Mishima Kazuo  秋田大学, 医学系研究科, 教授 (40239223)

Research Collaborator Hida Akiko  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywords睡眠障害 / 概日リズム / メチル化 / エピゲノム / 生理学 / 睡眠学 / 時間生物学 / 睡眠 / 生体リズム / 加齢 / 睡眠科学
Outline of Final Research Achievements

We performed polysomnography, circadian rhythm measurement and blood sampling for methylation typing (8 points every 4 hours) for 48 hours for healthy young adults and healthy elderly people over 60 years old. Methylation typing of the entire genome was performed by the microarray system using the Infinium Methylation EPIC BeadChip kit equipped with the 866,895 markers. In order to identify the methylated region involved in sleep and biological rhythm regulatory functions, the time series change of the obtained methylation amount was analyzed by the cosinor method. As a result, there were 16 regions where circadian rhythmicity was recognized in both young and elderly people. These methylation sites could be essential for the formation of circadian signal irrespective of age.

Academic Significance and Societal Importance of the Research Achievements

本研究の目的は、睡眠の質的量的低下や内的脱同調などの睡眠・生体リズム調節障害が高齢者の認知機能や気分調節に及ぼす影響を精密に評価し、その罹患脆弱性や個人差が生じる生理・分子的基盤を遺伝要因と環境要因の相互作用の視点から明らかにすることにある。また、睡眠・生体リズムを効果的に調整するための生活習慣の確立とその奏功メカニズム、高齢者の頑健な睡眠機能の生理的意義の解明に資する基盤データを得ることにある。本研究により概日リズム制御に関わる可能性のあるメチル化領域が明らかになった。今後、睡眠・概日リズム障害を呈する疾患患者を対象にして同候補領域におけるメチル化機能の変化を追跡する。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (6 results)

All 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] A variant at 9q34.11 is associated with HLA-DQB1*06:02 negative essential hypersomnia2018

    • Author(s)
      Miyagawa T, Khor SS, Toyoda H, Kanbayashi T, Imanishi A, Sagawa Y, Kotorii N, Kotorii T, Ariyoshi Y, Hashizume Y, Ogi K, Hiejima H, Kamei Y, Hida A, et al.
    • Journal Title

      J Hum Genet

      Volume: 63 Issue: 12 Pages: 1259-1267

    • DOI

      10.1038/s10038-018-0518-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lack of association between PER3 variable number tandem repeat and circadian rhythm sleep-wake disorders2018

    • Author(s)
      Hida A, Kitamura S, Kadotani H, Uchiyama M, Ebisawa T, Inoue Y, Kamei Y, Mishima K
    • Journal Title

      Human Genome Variation

      Volume: 5 Issue: 1 Pages: 17-17

    • DOI

      10.1038/s41439-018-0017-7

    • NAID

      120006539730

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two days’ sleep debt causes mood decline during resting state via diminished amygdala-prefrontal connectivity2017

    • Author(s)
      Motomura Yuki、Katsunuma Ruri、Yoshimura Michitaka、Mishima Kazuo
    • Journal Title

      Sleep

      Volume: 40

    • DOI

      10.1093/sleep/zsx133

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of circadian phenotypes utilizing fibroblasts from patients with circadian rhythm sleep disorders2017

    • Author(s)
      A Hida, Y Ohsawa, S Kitamura, K Nakazaki, N Ayabe, Y Motomura, K Matsui, M Kobayashi, A Usui, Y Inoue, H Kusanagi, Y Kamei, K Mishima
    • Journal Title

      Transl Psychiatry

      Volume: 7 Issue: 4 Pages: e1106-e1106

    • DOI

      10.1038/tp.2017.75

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Pathophysiology and strategic treatment of sighted non-24-h sleep-wake rhythm disorders2017

    • Author(s)
      Mishima K
    • Journal Title

      Sleep and Biological Rhythms

      Volume: 15 Issue: 1 Pages: 11-20

    • DOI

      10.1007/s41105-016-0076-4

    • NAID

      40021060417

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] Screening for genetic variations associated with circadian rhythm sleep-wake disorders2017

    • Author(s)
      K Mishima, A Hida
    • Organizer
      The 2017 joint congress of World Association of Sleep Medicine and World Sleep Federation
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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