Elucidation of performance-associated functional polymorphisms in sprinters and endurance runners in the world and Japan

2015 Fiscal Year Annual Research Report

• Project/Area Number: 25242062
• 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): 2013-04-01 – 2016-03-31
• Keywords: 全ゲノム領域塩基配列 / アスリート / 運動能力 / 遺伝子多型

Outline of Annual Research Achievements

本研究の目的は、世界ならびに日本のトップアスリートの瞬発系および持久系運動能力に影響を与えている全エクソン領域に存在するアミノ酸置換を伴う機能的多型の網羅的解析を行い、運動能力に関連する遺伝子多型を探索することにある。これによって骨格筋の代謝的特性ならびに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し、個人の特性に応じた競技種目の選択や予後予測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と期待される。Illumina社のInfinium HumanExome BeadChipを用いて、約24万個のアミノ酸置換を伴う機能的多型を網羅的に解析した。必要なDNA量を確保するために、予めwhole genome amplificationを実施した。Jamaicaのアスリート93人と対照群306人、USAのアスリート112人と対照群200人、合計711人の試料についてBeadChip解析を終えた。このうち、レジェンド・アスリートは48人、国際大会への出場経験のあるアスリートは91人であった。日本人対照群として、平成25年度に2268人、平成26年度に913人、平成27年度に969人に関して、全エクソン領域の機能的多型を同一のBeadChipを用いて解析した。Whole genome amplification後のDNAを用いてBeadChip解析を行うと、標準クラスターを用いてgenotypingを行うことが困難であった。カスタム・クラスターを使用しても判定不能となる一塩基多型が多発した。新しい次世代シークエンサー（Illumina社HiSeq X）によって全ゲノム領域塩基配列を決定する方針に変更した。このために、解析対象としてエチオピアから8人、ケニアから8人を厳選し、DNAを頬粘膜擦過試料から再抽出し、全ゲノム領域塩基配列を決定した。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [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] 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: 印刷中 Pages: 印刷中
  • DOI: 10.18632/oncotarget.16536
  • 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: 印刷中 Pages: 印刷中
  • DOI: 10.18632/oncotarget.16696
  • 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: 印刷中 Pages: 印刷中
  • DOI: 10.18632/oncotarget.16945
  • 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: 39 Pages: 1477-1491
  • DOI: 10.3892/ijmm.2017.2972
  • 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: 印刷中 Pages: 印刷中
  • DOI: in print
  • 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: 印刷中 Pages: 印刷中
  • DOI: 10.18632/oncotarget.17159
  • 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: 印刷中 Pages: 印刷中
  • DOI: in print
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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: 印刷中 Pages: 印刷中
  • DOI: in print
  • Peer Reviewed / 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: 316 Pages: 316
  • DOI: 10.1186/s12885-017-3301-x
  • Peer Reviewed / Open Access
• [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, Masashi Tanaka, et al.
  • Journal Title: J Gerontol A Biol Sci Med Sci Volume: 72 Pages: 309-318
  • DOI: 10.1093/gerona/glw074
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 健康長寿ゲノム探索研究と超高齢者疾患の遺伝学的解析 ―長寿あるいは運動能力に関連するゲノム多型― (2017)
  • Author(s): 田中雅嗣
  • Journal Title: 肝胆膵 Volume: 73 Pages: 341-347
• [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 / Acknowledgement Compliant
• [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 / Open Access
• [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 / Acknowledgement Compliant
• [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, et al.
  • Journal Title: Physiol Genomics Volume: 48 Pages: 183-190
  • DOI: 10.1152/physiolgenomics.00105.2015
  • 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: Phys Fitness Sports Med Volume: 5 Pages: 001-012
  • DOI: 10.7600/jpfsm.5.000
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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 / Open Access / Acknowledgement Compliant
• [Journal Article] GDF15 is a novel biomarker to evaluate efficacy of pyruvate therapy for mitochondrial diseases (2015)
  • Author(s): Yasunori Fujita, Masafumi Ito, Toshio Kojima, Shuichi Yatsuga, Yasutoshi Koga, Masashi Tanaka
  • Journal Title: Mitochondrion Volume: 20 Pages: 34-42
  • DOI: 10.1016/j.mito.2014.10.006
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A missense single nucleotide polymorphism, V114I of the Werner syndrome gene, is associated with risk of osteoporosis and femoral fracture in the Japanese population (2015)
  • Author(s): Heying Zhou, Seijiro Mori, Masashi Tanaka, Motoji Sawabe, Tomio Arai, Masaaki Muramatsu, Makiko Naka Mieno, Shoji Shinkai, Yoshiji Yamada, Motohiko Miyachi, Haruka Murakami, Kiyoshi Sanada, Hideki Ito
  • Journal Title: J Bone Miner Metab Volume: 33 Pages: 694-700
  • DOI: 10.1007/s00774-014-0636-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of the chromodomain helicase DNA-binding protein 4 (CHD4) missense variation p.D140E with cancer: potential interaction with smoking (2015)
  • Author(s): Miki Yamada, Noriko Sato, Shinobu Ikeda, Tomio Arai, Motoji Sawabe, Seijiro Mori, Yoshiji Yamada, Masaaki Muramatsu, Masashi Tanaka
  • Journal Title: Genes Chromosomes Cancer Volume: 54 Pages: 122-128
  • DOI: 10.1002/gcc.22227
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 10-Hydroxy-2-decenoic Acid, the major lipid component of royal jelly, extends the lifespan of Caenorhabditis elegans through dietary restriction and target of Rapamycin signaling (2015)
  • Author(s): Yoko Honda, Yoko Araki, Taketoshi Hata, Kenji Ichihara, Masahumi Ito, Masashi Tanaka, Shuji Honda
  • Journal Title: Journal of Aging Research Volume: 2015 Pages: ID 425261
  • DOI: 10.1155/2015/425261
  • Peer Reviewed / Open Access
• [Journal Article] Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies (2015)
  • Author(s): Daisuke Nishizawa, Masashi Tanaka et al.
  • Journal Title: Mol Brain Volume: 8 Pages: 50
  • DOI: 10.1186/s13041-015-0142-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Useful biomarker for mitochondrial disorders (2015)
  • Author(s): Shuichi Yatsuga, Yasunori Fujita, Akiko Ishii, Yoshihiro Fukumoto, Hajime Arahata, Tatsuyuki Kakuma, Toshio Kojima, Masafumi Ito, Masashi Tanaka, Reo Saiki, Yasutoshi Koga
  • Journal Title: Ann Neurol Volume: 78 Pages: 814-23
  • DOI: 10.1002/ana.24506
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Polygenic risk for hypertriglyceridemia is attenuated in Japanese men with high fitness levels (2015)
  • Author(s): Kumpei Tanisawa, Tomoko Ito, Xiaomin Sun, Zhen-Bo Cao, Shizuo Sakamoto, Masashi Tanaka, Mitsuru Higuchi
  • Journal Title: Physiol Genomics Volume: 46 Pages: 207-215
  • DOI: 10.1152/physiolgenomics.00182.2013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] High cardiorespiratory fitness can reduce glycated hemoglobin levels regardless of polygenic risk for type 2 diabetes mellitus in non-diabetic Japanese men (2015)
  • Author(s): Kumpei Tanisawa, Tomoko Ito, Xiaomin Sun, Ryuken Ise, Satomi Oshima, Zhen-Bo Cao, Shizuo Sakamoto, Masashi Tanaka, Mitsuru Higuchi
  • Journal Title: Physiol Genomics Volume: 46 Pages: 497-504
  • DOI: 10.1152/physiolgenomics.00027.2014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Strong influence of dietary intake and physical activity on body fatness in elderly Japanese men: age-associated loss of polygenic resistance against obesity (2015)
  • Author(s): Kumpei Tanisawa, Tomoko Ito, Xiaomin Sun, Ryuken Ise, Satomi Oshima, Zhen-Bo Cao, Shizuo Sakamoto, Masashi Tanaka, Mitsuru Higuchi
  • Journal Title: Genes Nutr Volume: 9 Pages: 416
  • DOI: 10.1007/s12263-014-0416-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ACTN3 R577X genotype is associated with sprinting in elite Japanese athletes (2015)
  • Author(s): E Mikami, N Fuku, H Murakami, H Tsuchie, H Takahashi, N Ohiwa, H Tanaka, Y P Pitsiladis, M Higuchi, M Miyachi, T Kawahara, Masashi Tanaka
  • Journal Title: Intl J Sports Med Volume: 35 Pages: 172-177
  • DOI: 10.1055/s-0033-1347171
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Evolution of mitochondrial power in vertebrate metazoans (2015)
  • Author(s): Yasuhiro Kitazoe, Masashi Tanaka
  • Journal Title: PloS One Volume: 9 Pages: 6.06
  • DOI: 10.1371/journal.pone.0098188
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] New MT-ND6 and NDUFA1 mutations in mitochondrial respiratory chain disorders (2015)
  • Author(s): Natsumi Uehara, Masato Mori, Yoshimi Tokuzawa, Yosuke Mizuno, Yasunori Fujita, Masafumi Ito, Masashi Tanaka, Ken-ichi Nibu, Akira Ohtake, Yasushi Okazaki
  • Journal Title: Ann Clin Transl Neurol Volume: 1 Pages: 361-369
  • DOI: 10.1002/acn3.59
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Efficacy of pyruvate therapy in patients with mitochondrial disease: A semi-quantitative clinical evaluation study (2015)
  • Author(s): Tatsuya Fujii, Fumihito Nozaki, Keiko Saito, Anri Hayashi, Yutaka Nishigaki, Kei Murayama, Masashi Tanaka, Yasutoshi Koga, Ikuko Hiejima, Tomohiro Kumada
  • Journal Title: Mol Genet Metab Volume: 112 Pages: 133-138
  • DOI: 10.1016/j.ymgme.2014.04.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 7501T>A mitochondrial DNA variant in a patient with glomerulosclerosis (2015)
  • Author(s): Toshiyuki Imasawa, Masashi Tanaka, Yutaka Yamaguchi, Takashi Nakazato, Hiroshi Kitamura, Motonobu Nishimura
  • Journal Title: Ren Fail Volume: 36 Pages: 1461-1465
  • DOI: 10.3109/0886022X.2014.945181
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pathological similarities between low birth weight-related nephropathy and nephropathy associated with mitochondrial cytopathy (2015)
  • Author(s): Toshiyuki Imasawa, Masashi Tanaka, Naoki Maruyama, Takehiko Kawaguchi, Yutaka Yamaguchi, Rodrigue Rossignol, Hiroshi Kitamura, Motonobu Nishimura
  • Journal Title: Diagn Pathol Volume: 9 Pages: 181
  • DOI: 10.1186/s13000-014-0181-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] The 1000 Athlomes Project: 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: ICSEMIS 2016 (International Council of Sport Science and Physical Education)
  • 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