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DNA methylation signatures of peripheral leukocytes in schizophrenia

Research Project

Project/Area Number 24791216
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Psychiatric science
Research InstitutionThe University of Tokushima

Principal Investigator

NUMATA Shusuke  徳島大学, 大学病院, 講師 (10403726)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsschizophrenia, / DNA methylation / epigenetic / microarray / monozygotic twins / DNAメチル化 / 統合失調症 / 診断マーカー / バイオマーカー / 血液 / ホモシステイン / schizophrenia / array
Research Abstract

Genome-wide DNA methylation profiling (485,764 CpG sites) of peripheral leukocytes was conducted in the first set of samples (24 medication-free patients with SCZ and 23 non-psychiatric controls) using Infinium HumanMethylation450 Beadchips. Second, a monozygotic twin study was performed using three pairs of monozygotic twins that were discordant for SCZ. Finally, the data from these two independent cohorts were compared.A total of 234 differentially methylated CpG sites that were common between these two cohorts were identified. Of the 234 CpG sites, 153 sites (65.4%) were located in the CGIs and in the regions flanking CGIs (CGI: 40.6%; CGI shore: 13.2%; CGI shelf: 11.5%). Of the 95 differently methylated CpG sites in CGIs, most of them were located in the promoter regions (promoter: 75.8%; gene body: 14 .7%; 3'UTR: 2.1%). Aberrant DNA methylation in SCZ was identified at numerous loci across the whole genome in peripheral leukocytes.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (49 results)

All 2014 2013 2012

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (34 results) (of which Invited: 5 results) Book (5 results)

  • [Journal Article] Microarray analysis of global gene expression in leukocytes following lithium treatment.2014

    • Author(s)
      Watanabe S, Iga J, Nishi A, Numata S, Kinoshita M, Kikuchi K, Nakataki M, Ohmori T.
    • Journal Title

      Hum Psychopharmacol.

      Volume: 29 Issue: 2 Pages: 190-198

    • DOI

      10.1002/hup.2381

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] An evaluation of association between a novel hippocampal biology related SNP (rs7294919) and schizophrenia2013

    • Author(s)
      Liu, J., Numata, S., Ikeda, M., Watanabe, Y., Zheng, X., Luo, X., Kinoshita, M., Nunokawa, A., Someya, T., Ohmori, T., Bei, J., Chong, S., Lee, J., Li, Z., Liu, J., Iwata, N., Shi, Y., Li, M., Su, B
    • Journal Title

      PLoS One

      Volume: 8 Issue: 11 Pages: e80696-e80696

    • DOI

      10.1371/journal.pone.0080696

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia. Epigenetics2013

    • Author(s)
      Kinoshita M, Numata S, Tajima A, Shimodera S, Imoto I, Ohmori T
    • Journal Title

      Epigenetics

      Volume: 8(6) Issue: 6 Pages: 584-590

    • DOI

      10.4161/epi.24621

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA methylation signatures of peripheral leukocytes in schizophrenia2013

    • Author(s)
      Kinoshita M, Numata S, Tajima A, Shimodera S, Ono S, Imamura A, Iga JI, Watanabe S, Kikuchi K, Kubo H, Nakataki M, Sumitani S, Imoto I, Okazaki Y, Ohmori T
    • Journal Title

      Neuromolecular Med

      Volume: 15(1) Issue: 1 Pages: 95-101

    • DOI

      10.1007/s12017-012-8198-6

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genetic evidence for association between NOTCH4 and schizophrenia supported by a GWAS follow-up study in a Japanese population2013

    • Author(s)
      Ikeda M, Aleksic B, Yamada K, Iwayama-Shigeno Y, Matsuo K, Numata S, Watanabe Y, Ohnuma T, Kaneko T, Fukuo Y, Okochi T, Toyota T, Hattori E, Shimodera S, Itakura M, Nunokawa A, Shibata N, Tanaka H, Yoneda H, Arai H, Someya T, Ohmori T, Yoshikawa T, Ozaki N, Iwata N
    • Journal Title

      Mol Psychiatry

      Volume: 18(6) Issue: 6 Pages: 636-638

    • DOI

      10.1038/mp.2012.74

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association Study of Fat-mass and Obesity-associated Gene and Body Mass Index in Japanese Patients with Schizophrenia and Healthy Subjects2012

    • Author(s)
      Watanabe SY
    • Journal Title

      Clin Psychopharmacol Neurosci

      Volume: 10 Issue: 3 Pages: 185-189

    • DOI

      10.9758/cpn.2012.10.3.185

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical correlates associated with cognitive dysfunction in people with schizophrenia2012

    • Author(s)
      Tanaka T, Tomotake M, Ueoka Y, Kaneda Y, Taniguchi K, Nakataki M, Numata S, Tayoshi S, Yamauchi K, Sumitani S, Ohmori T, Ueno S, Ohmori T
    • Journal Title

      Psychiatry Clin Neurosci

      Volume: 66(6) Issue: 6 Pages: 491-8

    • DOI

      10.1111/j.1440-1819.2012.02390.x

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Meta-analysis of association studies between DISC1 missense variants and schizophrenia in Japanese population.2012

    • Author(s)
      Kinoshita M, et al
    • Journal Title

      Schizophr Res,

      Volume: 141(2-3): Issue: 2-3 Pages: 271-273

    • DOI

      10.1016/j.schres.2012.07.020

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A commentary on the gender-specific association of TSNAX/DISC1 locus for schizophrenia and bipolar affective disorder in South Indian population2012

    • Author(s)
      Numata S
    • Journal Title

      J Hum Genet

      Volume: 57(8) Issue: 8 Pages: 475-476

    • DOI

      10.1038/jhg.2012.82

    • NAID

      10031056329

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Functional genetic variation at the NRGN gene and schizophrenia: Evidence from a gene-based case-control study and gene expression analysis2012

    • 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

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 血漿ホモシステイン濃度に影響を与える機能性多型の統合失調症遺伝子関連研究2014

    • Author(s)
      木下誠, 沼田周助, 土屋篤司, 村木翔, 西晃, 田嶋敦, 井本逸勢, 大森哲郎
    • Organizer
      第9回日本統合失調症学会
    • Place of Presentation
      京都テレサ, 京都府
    • Year and Date
      2014-03-14
    • Related Report
      2013 Final Research Report
  • [Presentation] 統合失調症における血漿ホモシステイン濃度とDNA メチル化修飾~ビタミン投与による治療の可能性を探る~2014

    • Author(s)
      沼田周助
    • Organizer
      ビタミンB研究委員会
    • Place of Presentation
      大阪大学中之島センター, 大阪府
    • Year and Date
      2014-01-31
    • Related Report
      2013 Final Research Report
  • [Presentation] 統合失調症における血漿ホモシステイン濃度DNAメチル化修飾~ビタミン投与による治療の可能性を探る2014

    • Author(s)
      沼田周助
    • Organizer
      ビタミンB研究委員会
    • Place of Presentation
      大阪大学中之島センター、大阪府
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 血漿ホモシステイン濃度に影響を与える機能性多型の統合失調症遺伝子関連研究2014

    • Author(s)
      木下誠、沼田周助、土屋篤司、村木翔、西晃、田嶋敦、井本逸勢、大森哲郎
    • Organizer
      第9回日本統合失調症学会
    • Place of Presentation
      京都テルサ、京都府
    • Related Report
      2013 Annual Research Report
  • [Presentation] Total plasma homocysteine and schizophrenia : gender and MTHFR C677T genotypes2013

    • Author(s)
      Akira Nishi, Shusuke Numata, Atsushi Tajima, Kumiko Kikuchi, Makoto Kinoshita, Shinji Shimodera, Masahito Tomotake, Issei Imoto, and Tetsuro Ohmori
    • Organizer
      Neuroscience 2013
    • Place of Presentation
      San Diego Convention Center, USA
    • Year and Date
      2013-11-09
    • Related Report
      2013 Final Research Report
  • [Presentation] The effect of MTHFR C677T on DNA methylation of peripheral leukocytes in schizophrenia2013

    • Author(s)
      Makoto Kinoshita, Shusuke Numata, Atsushi Tajima, Kazutaka Ohi, Ryota Hashimoto, Shinji Shimodera, Issei Imoto, Masatoshi Takeda and Tetsuro Ohmori
    • Organizer
      Neuroscience 2013
    • Place of Presentation
      San Diego Convention Center, USA
    • Year and Date
      2013-11-09
    • Related Report
      2013 Final Research Report
  • [Presentation] 治療抵抗性統合失調症のバイオマーカー2013

    • Author(s)
      沼田周助, 木下誠, 田嶋敦, 下寺信次, 橋本亮太, 井本逸勢, 武田雅俊, 大森哲郎
    • Organizer
      第23回日本臨床精神神経薬理学会
    • Place of Presentation
      沖縄コンベンションセンター, 沖縄県
    • Year and Date
      2013-10-24
    • Related Report
      2013 Final Research Report
  • [Presentation] ゲノム・ワイドメチル化解析からみた統合失調症の病態2013

    • Author(s)
      沼田周助, 木下誠, 大森哲郎
    • Organizer
      第23回日本臨床精神神経薬理学会
    • Place of Presentation
      沖縄コンベンションセンター, 沖縄県
    • Year and Date
      2013-10-24
    • Related Report
      2013 Final Research Report
  • [Presentation] Structural brain asymmetry in obsessive-compulsive disorder2013

    • Author(s)
      Masahito Nakataki, Satsuki Sumitani, Hiroko Kubo, Shusuke Numata, Jun-Ichi Iga, Shin-Ya Watanabe, Makoto Kinoshita, Masafumi Harada, Tetsuro Ohmori
    • Organizer
      11th world congress of biological psychiatry
    • Place of Presentation
      Kyoto International Conference Center, 京都府
    • Year and Date
      2013-06-23
    • Related Report
      2013 Final Research Report
  • [Presentation] A gender-specific meta-analysis2013

    • Author(s)
      Shu-Suke Numata, Kumiko Kikuchi, Atsushi Tajima, Makoto Kinoshita, Shinji Shimodera, Masahito Tomotake, Issei Imoto, Tetsuro Ohmori. Plasma homocysteine and schizophrenia
    • Organizer
      11th world congress of biological psychiatry
    • Place of Presentation
      Kyoto International Conference Center, 京都府
    • Year and Date
      2013-06-23
    • Related Report
      2013 Final Research Report
  • [Presentation] Genome-wide association study of plasma homocysteine and DNA methylation in patients with schizophrenia2013

    • Author(s)
      Makoto Kinoshita, Shusuke Numata, Atsushi Tajimia, Shinji Shimodera, Issei Imoto, Tetsuro Ohmori
    • Organizer
      11th world congress of biological psychiatry
    • Place of Presentation
      Kyoto International Conference Center, 京都府
    • Year and Date
      2013-06-23
    • Related Report
      2013 Final Research Report
  • [Presentation] Genome-wide methylation status of human leukocytes in mood disorders2013

    • Author(s)
      Shu-Suke Numata, Makoto Kinoshita, Atsushi Tajima, Shinji Shimodera, Jun-ichi Iga, Shinya Watanabe, Issei Imoto, Tetsuro Ohmori
    • Organizer
      11th world congress of biological psychiatry
    • Place of Presentation
      Kyoto International Conference Center, 京都府
    • Year and Date
      2013-06-23
    • Related Report
      2013 Final Research Report
  • [Presentation] Biological diagnostic test for major depressive disorder based on the leukocytes gene expression : Preliminary study2013

    • Author(s)
      Shinya Watanabe, Jun-Ichi Iga, Shusuke Numata, Makoto Kinoshita, Tetsuro Ohmori
    • Organizer
      11th world congress of biological psychiatry
    • Place of Presentation
      Kyoto International Conference Center, 京都府
    • Year and Date
      2013-06-23
    • Related Report
      2013 Final Research Report
  • [Presentation] DNA Methylation Signatures of Prefrontal Cortex and Peripheral Leukocytes in Schizophrenia2013

    • Author(s)
      Shusuke Numata
    • Organizer
      Society of Biological Psychiatry 68th Annual Meeting
    • Place of Presentation
      Hilton Hotel, USA
    • Year and Date
      2013-05-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 統合失調症における末梢血DNA メチル化修飾解析研究2013

    • Author(s)
      沼田周助, 木下誠, 田嶋敦, 下寺信次, 橋本亮太, 武田雅俊, 井本逸勢, 大森哲郎
    • Organizer
      第8回日本統合失調症学会
    • Place of Presentation
      浦河町総合文化会館, 北海道
    • Year and Date
      2013-04-19
    • Related Report
      2013 Final Research Report
  • [Presentation] DNA Methylation Signatures of Prefrontal Cortex and Peripheral Leukocytes in Schizophrenia2013

    • Author(s)
      Shusuke Numata
    • Organizer
      Society of Biological Psychiatry 68th Annual Meeting
    • Place of Presentation
      Hilton hotel, USA
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Structural brain asymmetry in obsessive-compulsive disorder.2013

    • Author(s)
      Masahito Nakataki, Satsuki Sumitani, Hiroko Kubo, Shusuke Numata, Jun-Ichi Iga, Shin-Ya Watanabe, Makoto Kinoshita, Masafumi Harada, Tetsuro Ohmori
    • Organizer
      11th world congress of biological psychiatry
    • Place of Presentation
      Kyoto International Conference Center、京都府
    • Related Report
      2013 Annual Research Report
  • [Presentation] Plasma homocysteine and schizophrenia: A gender-specific meta-analysis.2013

    • Author(s)
      Shu-Suke Numata, Kumiko Kikuchi, Atsushi Tajima, Makoto Kinoshita, Shinji Shimodera, Masahito Tomotake, Issei Imoto, Tetsuro Ohmori
    • Organizer
      11th world congress of biological psychiatry
    • Place of Presentation
      Kyoto International Conference Center、京都府
    • Related Report
      2013 Annual Research Report
  • [Presentation] Genome-wide association study of plasma homocysteine and DNA methylation in patients with schizophrenia.2013

    • Author(s)
      Makoto Kinoshita, Shusuke Numata, Atsushi Tajimia, Shinji Shimodera, Issei Imoto, Tetsuro Ohmori.
    • Organizer
      11th world congress of biological psychiatry
    • Place of Presentation
      Kyoto International Conference Center、京都府
    • Related Report
      2013 Annual Research Report
  • [Presentation] Genome-wide methylation status of human leukocytes in mood disorders.2013

    • Author(s)
      Shu-Suke Numata, Makoto Kinoshita, Atsushi Tajima, Shinji Shimodera, Jun-ichi Iga, Shinya Watanabe, Issei Imoto, Tetsuro Ohmori
    • Organizer
      11th world congress of biological psychiatry
    • Place of Presentation
      Kyoto International Conference Center、京都府
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Biological diagnostic test for major depressive disorder based on the leukocytes gene expression: Preliminary study.2013

    • Author(s)
      Shinya Watanabe, Jun-Ichi Iga, Shusuke Numata, Makoto Kinoshita, Tetsuro Ohmori.
    • Organizer
      11th world congress of biological psychiatry
    • Place of Presentation
      Kyoto International Conference Center、京都府
    • Related Report
      2013 Annual Research Report
  • [Presentation] Total plasma homocysteine and schizophrenia: gender and MTHFR C677T genotypes.2013

    • Author(s)
      Akira Nishi, Shusuke Numata, Atsushi Tajima, Kumiko Kikuchi, Makoto Kinoshita, Shinji Shimodera, Masahito Tomotake, Issei Imoto, and Tetsuro Ohmori
    • Organizer
      Society of Nueroscience
    • Place of Presentation
      San Diego Convention Center , USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] The effect of MTHFR C677T on DNA methylation of peripheral leukocytes in schizophrenia.2013

    • Author(s)
      Makoto Kinoshita, Shusuke Numata, Atsushi Tajima, Kazutaka Ohi, Ryota Hashimoto, Shinji Shimodera, Issei Imoto, Masatoshi Takeda and Tetsuro Ohmori.
    • Organizer
      Society of Nueroscience
    • Place of Presentation
      San Diego Convention Center , USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 統合失調症における末梢血DNAメチル化修飾解析研究2013

    • Author(s)
      沼田周助、木下誠、田嶋敦、下寺信次、橋本亮太、武田雅俊、井本逸勢、大森哲郎
    • Organizer
      第8回日本統合失調症学会
    • Place of Presentation
      浦河町総合文化会館、北海道
    • Related Report
      2013 Annual Research Report
  • [Presentation] 治療抵抗性統合失調症のバイオマーカー2013

    • Author(s)
      沼田周助、木下誠、田嶋敦、下寺信次、橋本亮太、井本逸勢、武田雅俊、大森哲郎
    • Organizer
      第23回日本臨床精神神経薬理学会
    • Place of Presentation
      沖縄コンベンションセンター、沖縄県
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ゲノム・ワイドメチル化解析からみた統合失調症の病態2013

    • Author(s)
      沼田周助、木下誠、大森哲郎
    • Organizer
      第23回日本臨床精神神経薬理学会
    • Place of Presentation
      沖縄コンベンションセンター、沖縄県
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 白血球遺伝子発現を指標としたリチウムの精神薬理学的研究2012

    • Author(s)
      伊賀淳一, 渡部真也, 西晃, 沼田周助, 木下誠, 中瀧理仁, 大森哲郎
    • Organizer
      第22回日本臨床精神神経薬理学会
    • Place of Presentation
      栃木県総合文化センター, 栃木県
    • Year and Date
      2012-10-18
    • Related Report
      2013 Final Research Report
  • [Presentation] Blood-based DNA methylation biomarkers for schizophrenia2012

    • Author(s)
      Shusuke Numata, Makoto Kinoshita, , Atsushi Tajima, Shinji Shimodera, Jun-ichi Iga, Shinya Watanabe, Issei Imoto, Tetsuro Ohmori
    • Organizer
      Neuroscience 2012
    • Place of Presentation
      Ernest N Morial Convention Center, USA
    • Year and Date
      2012-10-13
    • Related Report
      2013 Final Research Report
  • [Presentation] メタアナリシス解析を用いたDISC1 機能多型と統合失調症の遺伝子関連研究2012

    • Author(s)
      沼田周助, 木下誠, 田嶋敦, 大井一高, 橋本亮太, 下寺信次, 井本逸勢, 武田雅俊, 大森哲郎
    • Organizer
      第34回日本生物学的精神医学会
    • Place of Presentation
      神戸国際会議場, 兵庫県
    • Year and Date
      2012-09-28
    • Related Report
      2013 Final Research Report
  • [Presentation] Genome-wide DNA methylation analysis using peripheral blood samples derived from unmedicated patients with schizophrenia2012

    • Author(s)
      Kinoshita M, Numata S, Tajima A, Watanabe S, Iga J, et al
    • Organizer
      28th CINP Congress
    • Place of Presentation
      Stockholmsmasssan, Sweden
    • Year and Date
      2012-06-03
    • Related Report
      2013 Final Research Report
  • [Presentation] Genome-wide DNA methylation analysis using peripheral blood samples derived from unmedicated patients with schizophrenia2012

    • Author(s)
      Kinoshita M, Numata S, et al.
    • Organizer
      28th CINP Congress
    • Place of Presentation
      Stockholmsmassan (Sweden)
    • Related Report
      2012 Research-status Report
  • [Presentation] Blood-based DNA methylation biomarkers for schizophrenia.2012

    • Author(s)
      Shusuke Numata, et al.
    • Organizer
      Neuroscience
    • Place of Presentation
      Ernest N. Morial Cobvention Center (USA)
    • Related Report
      2012 Research-status Report
  • [Presentation] メタアナリシス解析を用いたDISC1機能多型と統合失調症の遺伝子関連研究2012

    • Author(s)
      沼田周助、et al.
    • Organizer
      第34回日本生物学的精神医学会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Related Report
      2012 Research-status Report
  • [Presentation] 白血球遺伝子発現を指標としたリチウムの精神薬理学的研究2012

    • Author(s)
      伊賀淳一、et al.
    • Organizer
      第22回日本臨床精神神経薬理学会
    • Place of Presentation
      栃木県総合文化センター(栃木)
    • Related Report
      2012 Research-status Report
  • [Book] 開発中の薬剤の動向2013

    • Author(s)
      沼田周助, 大森哲郎
    • Total Pages
      270
    • Publisher
      ライフサイエンス
    • Related Report
      2013 Final Research Report
  • [Book] ガイドライン外来診察2013(統合失調症)2013

    • Author(s)
      沼田周助, 大森哲郎
    • Total Pages
      658
    • Publisher
      日経メディカル開発
    • Related Report
      2013 Final Research Report
  • [Book] ガイドライン外来診察2013(統合失調症)2013

    • Author(s)
      沼田周助、大森哲郎
    • Total Pages
      658
    • Publisher
      日経メディカル開発
    • Related Report
      2013 Annual Research Report
  • [Book] 開発中の薬剤の動向2013

    • Author(s)
      沼田周助、大森哲郎
    • Total Pages
      270
    • Publisher
      ライフ・サイエンス
    • Related Report
      2013 Annual Research Report
  • [Book] ガイドライン外来診療20132013

    • Author(s)
      沼田周助、大森哲郎
    • Publisher
      日経メディカル開発
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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