Elucidation of exercise performance-related genes by whole genome sequencing of world elite sprinters and long distance runners

2016 Fiscal Year Annual Research Report

• Project/Area Number: 16H01872
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: 田中 雅嗣 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 協力研究員 (60155166)
• Project Period (FY): 2016-04-01 – 2021-03-31
• Keywords: 全ゲノム塩基配列解析 / アスリート / 瞬発系運動能力 / 持久系運動能力

Outline of Annual Research Achievements

本研究の目的は、世界の瞬発系および持久系運動選手のゲノム全領域の塩基配列を次世代シークエンサによって決定し、遺伝子発現制御の特性、遺伝子産物の構造・機能に影響を与えるアミノ酸置換、さらにゲノムの構造変化を網羅的に解析することによって、運動能力に関連する遺伝的素因を解明することにある。骨格筋・血液細胞でのトランスクリプトーム・メタボローム等の解析結果との照合により、骨格筋の代謝的特性ならびに骨格筋・腱の強度に影響を与える多型、呼吸・循環系の適応能力に関連する遺伝的背景を明らかにすることができ、個人の特性に応じた競技種目の選択やトレーニング方法の改善などに役立てることができる。アスローム研究とは、アスリートのためのマルチオミクス研究 “Multi-Omics Studies for Athletes”であり、ゲノム・トランスクリプトーム・エピゲノム・プロテオーム・メタボローム “genome, transcriptome, epigenome, proteome, metabolome”を包括的に解析する。Athlome Project Consortiumは具体的に4つの目標を掲げる。1) 世界の研究拠点の相互協力体制とバイオバンクを構築する。2) 運動能力、トレーニングに対する応答、筋損傷易罹患性に関連する遺伝子多型を発見する。3) 探索的研究から得られた遺伝子マーカーの有用性を検証・確認する。4) 新たに発見された生物学的プロセスを理解するために遺伝子産物の機能解析を行う。
今年度は、イルミナ社のHiSeq X Fiveを用いて、ケニア人7人、エチオピア人8人の長距離選手の全ゲノム塩基配列を決定した。対照群として日本人1人のゲノムを3回解析し、塩基配列決定の再現性を確認した。

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

過去に集積されたDNAの質が低いため、高度な塩基配列解析に適さないサンプルが含まれていた。

Strategy for Future Research Activity

保存されているサンプルからのDNAの再抽出、ならびに唾液などサンプルの再採取を行うこととした。来年度には目標とするサンプル数を確保できる見通しとなった。

Research Products

• [Journal Article] Exome-wide association study identifies CLEC3B missense variant p.S106G as being associated with extreme longevity in East Asian populations (2017)
  • Author(s): Kumpei Tanisawa, Y. Arai, N. Hirose, H. Shimokata, Y. Yamada, H. Kawai, M. Kojima, S. Obuchi, H. Hirano, H. Yoshida, H. Suzuki, Y. Fujiwara, K. Ihara, M. Sugaya, T. Arai, S. Mori, M. Sawabe, N. Sato, M. Muramatsu, M. Higuchi, Y.-W. Liu, Qing-Peng Kong, Masashi Tanaka
  • Journal Title: J Gerontol A Biol Sci Med Sci 72: 3. Volume: 72 Pages: 309-318
  • DOI: 10.1093/gerona/glw074
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Gamma-glutamyltransferase activity in exosomes as a potential marker for prostate cancer (2017)
  • Author(s): Kyojiro Kawakami, Yasunori Fujita, Yoko Matsuda, Tomio Arai, Kengo Horie, Koji Kameyama, Taku Kato, Koichi Masunaga, Yutaka Kasuya, Masashi Tanaka, Kosuke Mizutani, Takashi Deguchi, Masafumi Ito
  • Journal Title: BMC Cancer Volume: in press Pages: －
  • Peer Reviewed / Open Access
• [Journal Article] Association of macrophage capping protein (CAPG) Arg335His polymorphism and cancer susceptibility in the elderly (2017)
  • Author(s): Sariya Dechamethakun, Noriko Sato, Shinobu Ikeda, Motoji Sawabe, Seijiro Mori, Yoshiji Yamada, Masashi Tanaka, Masaaki Muramatsu, Tomio Arai
  • Journal Title: J Gerontol Geriatr Res Volume: 6 Pages: 417
  • DOI: 10.4172/2167-7182.100417
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of TNFSF13, SPATC1L, SLC22A25, and SALL4 as novel susceptibility loci for atrial fibrillation by an exome-wide association study (2017)
  • Author(s): Yoshiji Yamada, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Masaaki Muramatsu, Motoji Sawabe, Yoshinori Fujiwara, Yu Taniguchi, Shuichi Obuchi, Hisashi Kawai, Shoji Shinkai, Seijiro Mori, Tomio Arai, Masashi Tanaka
  • Journal Title: Mol Med Rep Volume: (in press) Pages: －
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of eight genetic variants as novel determinants of dyslipidemia in Japanese by exome-wide association studies (2017)
  • Author(s): Yoshiji Yamada, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Masaaki Muramatsu, Motoji Sawabe, Yoshinori Fujiwara, Yu Taniguchi, Shuichi Obuchi, Hisashi Kawai, Shoji Shinkai, Seijiro Mori, Tomio Arai, Masashi Tanaka
  • Journal Title: Oncotarget Volume: (in press) Pages: －
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of polymorphisms in 12q24.1, ACAD10, and BRAP as novel genetic determinants of blood pressure in Japanese by exome-wide association studies (2017)
  • Author(s): Yoshiji Yamada, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Masaaki Muramatsu, Motoji Sawabe, Yoshinori Fujiwara, Yu Taniguchi, Shuichi Obuchi, Hisashi Kawai, Shoji Shinkai, Seijiro Mori, Tomio Arai, Masashi Tanaka
  • Journal Title: Oncotarget Volume: (in press) Pages: －
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of six polymorphisms as novel susceptibility loci for ischemic or hemorrhagic stroke by exome-wide association studies (2017)
  • Author(s): Yoshiji Yamada, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Masaaki Muramatsu, Motoji Sawabe, Yoshinori Fujiwara, Yu Taniguchi, Shuichi Obuchi, Hisashi Kawai, Shoji Shinkai, Seijiro Mori, Tomio Arai, Masashi Tanaka
  • Journal Title: Int J Mol Med Volume: (in press) Pages: －
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of rs7350481 at chromosome 11q23.3 as a novel susceptibility locus for metabolic syndrome in Japanese individuals by an exome-wide association study (2017)
  • Author(s): Yoshiji Yamada, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Masaaki Muramatsu, Motoji Sawabe, Yoshinori Fujiwara, Yu Taniguchi, Shuichi Obuchi, Hisashi Kawai, Shoji Shinkai, Seijiro Mori, Tomio Arai, Masashi Tanaka
  • Journal Title: Oncotarget Volume: (in press) Pages: －
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of C21orf59 and ATG2A as novel determinants of renal function-related traits in Japanese individuals by exome-wide association studies (2017)
  • Author(s): Yoshiji Yamada, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Masaaki Muramatsu, Motoji Sawabe, Yoshinori Fujiwara, Yu Taniguchi, Shuichi Obuchi, Hisashi Kawai, Shoji Shinkai, Seijiro Mori, Tomio Arai, Masashi Tanaka
  • Journal Title: Oncotarget Volume: (in press) Pages: －
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of STXBP2 as a novel susceptibility locus for myocardial infarction in Japanese individuals by an exome-wide association study (2017)
  • Author(s): Yoshiji Yamada, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Masaaki Muramatsu, Motoji Sawabe, Yoshinori Fujiwara, Yu Taniguchi, Shuichi Obuchi, Hisashi Kawai, Shoji Shinkai, Seijiro Mori, Tomio Arai, Masashi Tanaka
  • Journal Title: Oncotarget Volume: (in press) Pages: －
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of EGFLAM, SPATC1L, and RNASE13 as novel susceptibility loci for aortic aneurysm in Japanese individuals by exome-wide association studies (2017)
  • Author(s): Yoshiji Yamada, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Masaaki Muramatsu, Motoji Sawabe, Yoshinori Fujiwara, Yu Taniguchi, Shuichi Obuchi, Hisashi Kawai, Shoji Shinkai, Seijiro Mori, Tomio Arai, Masashi Tanaka
  • Journal Title: Int J Mol Med Volume: 39 Pages: 1091-1100
  • DOI: 10.3892/ijmm.2017.2927
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gene-exercise interactions in the development of cardiometabolic diseases (2016)
  • Author(s): Kumpei Tanisawa, Masashi Tanaka, Mitsuru Higuchi
  • Journal Title: J Phys Fitness Sports Med Volume: 5 Pages: 25-36
  • DOI: 10.7600/jpfsm.5.25
  • Peer Reviewed / Open Access
• [Journal Article] Association of non-synonymous variants in WIPF3 and LIPA genes with abdominal aortic aneurysm: an autopsy study (2016)
  • Author(s): Yuko Maeda, Noriko Sato, Makiko Naka-Mieno, Seijiro Mori, Tomio Arai, Masashi Tanaka, Masaaki Muramatsu, Motoji Sawabe
  • Journal Title: J Geriatr Cardiol Volume: 13 Pages: 960-967
  • DOI: 10.11909/j.issn.1671-5411.2016.12.003
  • Peer Reviewed / Open Access
• [Journal Article] Secreted growth differentiation factor 15 as a potential biomarker for mitochondrial dysfunctions in aging and age-related disorders (2016)
  • Author(s): Yasunori Fujita, Yu Taniguchi, Shoji Shinkai, Masashi Tanaka, Masafumi Ito
  • Journal Title: Geriatr Gerontol Int Volume: 16 Suppl 1 Pages: 17-29
  • DOI: 10.1111/ggi.12724
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Advancing sports and exercise genomics: moving from hypothesis-driven single study approaches to large multi-omics collaborative science (2016)
  • Author(s): Masashi Tanaka, Guan Wang, Yannis P Pitsiladis
  • Journal Title: Physiol Genomics Volume: 48 Pages: 173-174
  • DOI: 10.1152/physiolgenomics.00009.2016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] STED super-resolution imaging of mitochondria labeled with TMRM in living cells (2016)
  • Author(s): Masaya Ishigaki, Masumi Iketani, Maki Sugaya, Mayumi Takahashi, Masashi Tanaka, Seisuke Hattori, Ikuroh Ohsawa
  • Journal Title: Mitochondrion Volume: 28 Pages: 79-87
  • DOI: 10.1016/j.mito.2016.03.009
  • Peer Reviewed
• [Journal Article] Athlome Project Consortium: a concerted effort to discover genomic and other "omic" markers of athletic performance (2016)
  • Author(s): Yannis P Pitsiladis, Masashi Tanaka, Nir Eynon, Claude Bouchard, Kathryn N North, Alun G Williams, Malcolm Collins, Colin N Moran, Steven L Britton, Noriyuki Fuku, Euan A Ashley, Vassilis Klissouras, Alejandro Lucia, Ildus I Ahmetov, Eco de Geus, Mohammed Alsayrafi
  • Journal Title: Physiol Genomics Volume: 48 Pages: 183-190
  • DOI: doi: 10.1152/physiolgenomics.00105.2015
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] An Initiative for Whole Genome Sequencing of Elite Athletes (2016)
  • Author(s): Masashi Tanaka
  • Organizer: International Federation of Sports Medicine 34th WORLD CONGRESS OF SPORTS MEDICINE
  • Place of Presentation: Ljubljana, Slovenia
  • Year and Date: 2016-10-02 – 2016-10-02
  • Int'l Joint Research / Invited
• [Presentation] The 1000 Athlomes Project: An Initiative for Whole Genome Sequencing of Elite Athletes (2016)
  • Author(s): Masashi Tanaka
  • Organizer: International Convention on Science, Education and Medicine in Sport (ICSEMIS)
  • Place of Presentation: Santos, Brazil
  • Year and Date: 2016-08-31 – 2016-08-31
  • Int'l Joint Research / Invited
• [Book] テキスト健康科学 「遺伝と健康」 (2017)
  • Author(s): 田中雅嗣
  • Total Pages: 37-49
  • Publisher: 南江堂
• [Remarks] Human Mitochondrial Genome Polymorphism Database
  • URL: http://mtsnp.tmig.or.jp/mtsnp/index_e.shtml