Genome anthropology study for testing the Cold adaptation and Anti-Obesity hypothesis in East Asia

• Project/Area Number: 26291096
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Physical anthropology
• Research Institution: Jichi Medical University
• Principal Investigator: NAKAYAMA KAZUHIRO 自治医科大学, 医学部, 講師 (90433581)
• Co-Investigator(Kenkyū-buntansha): 渡邉 和寿 自治医科大学, 医学部, 助教 (60724416) ; 大橋 順 東京大学, 理学(系)研究科(研究院), 准教授 (80301141) ; 西村 貴孝 長崎大学, 医歯(薬)学総合研究科, 助教 (80713148)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: モンゴル人 / ゲノム多様性 / 寒冷適応 / 正の自然選択 / 肥満 / SNP / 進化遺伝学 / 人類学 / 遺伝学 / 社会医学 / 進化 / ゲノム / 熱産生 / 東アジア

Outline of Final Research Achievements

Obesity in modern humans is caused by the imbalance between energy intake and expenditure. Metabolic thermogenesis is enhanced by various stimuli including cold exposure and partly explains the energy expenditure in the human body. We hypothesized that the susceptibility to obesity in the present human populations consists of genotypes that had contributed to adaptation to cold environments during modern human evolution. To demonstrate this hypothesis, we promoted a multidisciplinary study integrating evolutionary genetics at genome wide level, genetic epidemiology, and molecular cellular biology.

Research Products

• [Journal Article] Evidence for Very Recent Positive Selection in Mongolian (2017)
  • Author(s): Nakayama K, Ohashi J, Watanabe K, Munkhtulga L, Iwamoto S.
  • Journal Title: Molecular Biology and Evolution Volume: 印刷中 Issue: 8 Pages: 1936-1946
  • DOI: 10.1093/molbev/msx138
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A missense variant, rs373863828-A (p.Arg457Gln), of CREBRF and body mass index in Oceanic populations. (2017)
  • Author(s): Naka I, Furusawa T, Kimura R, Natsuhara K, Yamauchi T, Nakazawa M, Ataka Y, Ishida T, Inaoka T, Matsumura Y, Ohtsuka R, Ohashi J
  • Journal Title: Journal of Human Genetics Volume: 印刷中 Issue: 9 Pages: 847-849
  • DOI: 10.1038/jhg.2017.44
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] An adaptive variant of TRIB2, rs1057001, is associated with higher expression levels of thermogenic genes in human subcutaneous and visceral adipose tissues (2017)
  • Author(s): Nakayama K, Iwamoto S
  • Journal Title: J Phyiol Anthropol Volume: 36 Issue: 1 Pages: 16-16
  • DOI: 10.1186/s40101-017-0132-z
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Influence of AHRR Pro189Ala polymorphism on kidney functions. Biosci Biotech Biochem. (2017)
  • Author(s): Nakayama K, Saito S, Watanabe K, Miyashita H, Nishijima F, Kamo Y, Tada K, Ishizuka S, Niwa T, Iwamoto S, Shimizu H
  • Journal Title: Biosci Biotech Biochem Volume: Published online Issue: 6 Pages: 1120-1124
  • DOI: 10.1080/09168451.2017.1292838
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ZNF70, a novel ILDR2-interacting protein, contributes to the regulation of HES1 gene expression (2016)
  • Author(s): Watanabe K, Nakayama K, Ohta S, Tago K, Boonvisut S, Millings EJ, Fischer SG, LeDuc CA, Leibel RL, Iwamoto S.
  • Journal Title: Biochem Biophys Res Commun Volume: 477 Issue: 4 Pages: 712-716
  • DOI: 10.1016/j.bbrc.2016.06.124
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Relationship between mitochondrial haplogroup and physiological responses to hypobaric hypoxia (2016)
  • Author(s): Motoi M, Nishimura T, Egashira Y, Kishida F, Watanuki S
  • Journal Title: J Physiol Anthropol Volume: 35 Issue: 1 Pages: 12-12
  • DOI: 10.1186/s40101-016-0094-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Replication analysis of genetic association of the NCAN-CILP2 region with plasma lipid levels and non-alcoholic fatty liver disease in Asian and Pacific ethnic groups. (2016)
  • Author(s): Boonvisut S, Nakayama K, Makishima S, Watanabe K, Miyashita H, Lkhagvasuren M,Kagawa Y, Iwamoto S
  • Journal Title: Lipids Health Dis. Volume: 15 Issue: 1 Pages: 8-8
  • DOI: 10.1186/s12944-016-0181-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Associations between a fatty acid desaturase gene polymorphism and blood arachidonic acid compositions in Japanese elderly. (2016)
  • Author(s): Horiguchi S, Nakayama K, Iwamoto S, Ishijima A, Minezaki T, Baba M, Kontai Y, Horikawa C, Kawashima H, Shibata H, Kagawa Y, Kawabata T.
  • Journal Title: Prostaglandins Leukot Essent Fatty Acids. Volume: 105 Pages: 9-14
  • DOI: 10.1016/j.plefa.2015.11.005
  • Peer Reviewed
• [Journal Article] The role of TRIB1 in lipid metabolism; from genetics to pathways. (2015)
  • Author(s): Iwamoto S, Boonvisut S, Makishima S, Ishizuka Y, Watanabe K, Nakayama K
  • Journal Title: Biochem Soc Trans. Volume: 43 Issue: 5 Pages: 1063-1068
  • DOI: 10.1042/bst20150094
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sin3A-associated protein, 18 kDa, a novel binding partner of TRIB1, regulates MTTP expression. (2015)
  • Author(s): Makishima S, Boonvisut S, Ishizuka Y, Watanabe K, Nakayama K, Iwamoto S.
  • Journal Title: J Lipid Res. Volume: 56 Issue: 6 Pages: 1145-1152
  • DOI: 10.1194/jlr.m057802
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients. (2015)
  • Author(s): Yang Z, Matsumoto A, Nakayama K, Jimbo EF, Kojima K, Nagata KI, et al.
  • Journal Title: Brain Dev. Volume: 15 Issue: 1 Pages: 91-9
  • DOI: 10.1016/j.braindev.2015.04.006
  • Peer Reviewed / Open Access
• [Journal Article] Genetic evidence for contribution of human dispersal to the genetic diversity of EBA-175 in Plasmodium falciparum (2015)
  • Author(s): Yoshiki Yasukochi, Izumi Naka, Jintana Patarapotikul, Hathairad Hananantachai, Jun Ohashi
  • Journal Title: Malaria Journal Volume: 14 Issue: 1 Pages: 293-293
  • DOI: 10.1186/s12936-015-0820-2
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Seasonal variation of non-shivering thermogenesis (NST) during mild cold exposure (2015)
  • Author(s): Nishimura T, Motoi M, Egashira Y, Choi D, Aoyagi K, Watanuki S.
  • Journal Title: Journal of Physiological Anthropology Volume: 34 Issue: 1 Pages: 11-11
  • DOI: 10.1186/s40101-015-0051-9
  • NAID: 120006987089
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Seasonal effects of the UCP3 and the RPTOR gene polymorphisms on obesity traits in Japanese adults. (2014)
  • Author(s): Nakayama K, Miyashita H, Iwamoto S
  • Journal Title: Journal of Physiological Anthropology Volume: 33 Issue: 1 Pages: 38-38
  • DOI: 10.1186/1880-6805-33-38
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Common variants of GIP are associated with visceral fat accumulation in Japanese adults. (2014)
  • Author(s): Nakayama K, Watanabe K, Boonvisut S, Makishima S, Miyashita H, Iwamoto S.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol. Volume: 307 Issue: 11 Pages: G1108-G1114
  • DOI: 10.1152/ajpgi.00282.2014
  • Peer Reviewed / Open Access
• [Journal Article] 健診集団試料を用いたMLXIPL Gln241His多型の適応的意義の検討 (2014)
  • Author(s): 中山 一大, 宮下 洋, 岩本禎彦
  • Journal Title: 日本生理人類学会誌 Volume: 19 Pages: 63-67
  • NAID: 110009818792
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of chronic leptin infusion on subsequent body weight and composition in mice: can body weight set point be reset? (2014)
  • Author(s): Watanabe K, Mueller BR, Skowronski AA, Rosenbaum M, Leibel RL
  • Journal Title: Molecular Metabolism Volume: 3 Issue: 4 Pages: 432-440
  • DOI: 10.1016/j.molmet.2014.02.003
  • Peer Reviewed / Open Access
• [Journal Article] Effects of a novel MC4R agonist on maintenance of reduced body weight in diet induced obese mice. (2014)
  • Author(s): 2.Skowronski AA, Morabito MV, Mueller BR, Lee S, Hjorth S, Lehmann A, Watanabe K, Zeltser LM, Ravussin Y, Rosenbaum M, Leduc CA, Leibel RL
  • Journal Title: Obesity Volume: 22 Issue: 5 Pages: 1287-1295
  • DOI: 10.1002/oby.20678
  • Peer Reviewed / Open Access
• [Journal Article] Beta cell dysfunction due to increased ER stress in a stem cell model of Wolfram syndrome. (2014)
  • Author(s): 3.Shang L, Hua H, Foo K, Martinez H, Watanabe K, Zimmer M, Kahler DJ, Freeby M, Chung W, LeDuc CA, Goland R, Leibel RL, and Dieter Egli
  • Journal Title: Diabetes Volume: 63 Issue: 3 Pages: 923-933
  • DOI: 10.2337/db13-0717
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between mitochondrial haplogroup and seasonal changes of physiological responses to cold. (2014)
  • Author(s): Nishimura T, Watanuki S.
  • Journal Title: Journal of Physiological Anthropology Volume: 33 Issue: 1 Pages: 27-27
  • DOI: 10.1186/1880-6805-33-27
  • NAID: 120006986366
  • Peer Reviewed / Open Access
• [Presentation] UCP1 genotype changes non-shivering thermogenesis under mild cold environment (2016)
  • Author(s): Nishimura T, Katsumura T, Motoi M, Oota H, Watanuki S
  • Organizer: Conference of "Modernization and Health in the Asia-Pacific Region"
  • Place of Presentation: Hilo, Hawaii, USA
  • Year and Date: 2016-08-19
  • Int'l Joint Research
• [Presentation] Detection of Population Specific Signals of Positive Selection in Mongolians (2016)
  • Author(s): Nakayama K, Ohash J, Munkhtulga L, Iwamoto S
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: 京都府京都市 京都国際会館
  • Int'l Joint Research
• [Presentation] ゲノムワイドSNP情報から表現型へのアプローチ：ヒトでの研究例を中心に (2016)
  • Author(s): 中山一大
  • Organizer: 日本比較臨床医学会第47回学術集会シンポジウム
  • Place of Presentation: 東京都武蔵野市 獣医生命科学大学
  • Invited
• [Presentation] 農耕・牧畜成立に関連するゲノム多様性－現代人の疾患感受性との関連で－ (2016)
  • Author(s): 中山一大
  • Organizer: 2016年度西洋史研究会大会
  • Place of Presentation: 宮城県仙台市 東北大学
  • Invited
• [Presentation] Identification of Genetic Variants for Visceral Fat Accumulation in Japanese. (2015)
  • Author(s): Nakayama K
  • Organizer: The 12th International Congress of Physiological Anthropology
  • Place of Presentation: 千葉県千葉市
  • Year and Date: 2015-10-29
  • Int'l Joint Research / Invited
• [Presentation] 高密度SNPジェノタイピングによるモンゴル人特異的な自然選択の検出 (2015)
  • Author(s): 中山一大, 大橋順、ルハグワスレン・ムンフトルガ、岩本禎彦
  • Organizer: 第69回日本人類学会大会
  • Place of Presentation: 東京都港区
  • Year and Date: 2015-10-11
• [Presentation] 寒冷適応に関わるUCP1 遺伝子型間のヒトにおける熱産生反応の違い (2015)
  • Author(s): 西村貴孝，勝村啓史，本井碧，太田博樹，綿貫茂喜
  • Organizer: 第69回日本人類学会大会
  • Place of Presentation: 東京都港区
  • Year and Date: 2015-10-11
• [Presentation] 新 規糖尿病感受性遺伝子Ildr2の機能解析 (2015)
  • Author(s): 渡邉和寿、中山 一大、Supichaya Boonvisut、Leibel Rudolph、岩本 禎彦
  • Organizer: 第58回日本糖尿病学会、
  • Place of Presentation: 山口県下関市
  • Year and Date: 2015-05-21
• [Presentation] Genetics of fat distribution and metabolism: Perspectives from human evolution (2015)
  • Author(s): Nakayama K
  • Organizer: International Symposium on Human Adaptation to Environment and Whole-body Coordination 2015
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-03-15
  • Invited
• [Presentation] アジア・オセアニア人における代謝特性の民族差の理解を目指したゲノムワイドSNP研究 (2014)
  • Author(s): 中山 一大、大橋順、香川靖雄、岩本禎彦
  • Organizer: 第68回日本人類学会大会
  • Place of Presentation: 静岡県浜松市
  • Year and Date: 2014-11-01
• [Presentation] Genetic variation of the Tribbles family and metabolic syndrome (2014)
  • Author(s): Nakayama K
  • Organizer: The 11the International Nikko Symposium
  • Place of Presentation: 栃木県下野市
  • Year and Date: 2014-10-30
• [Presentation] GIPおよびGIPRの遺伝的多型は日本人成人の内臓脂肪蓄積と関連する (2014)
  • Author(s): 中山一大、宮下洋、渡邉和寿、巻島咲穂、Boonvisut Supichay、岩本禎彦
  • Organizer: 第３５回日本肥満学会
  • Place of Presentation: 宮崎県宮崎市
  • Year and Date: 2014-10-25
• [Presentation] 新規糖尿病感受性遺伝子Ildr2の機能解析 (2014)
  • Author(s): 渡邉和寿、中山 一大、Leibel Rudolph、岩本 禎彦
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: 宮崎県宮崎市
  • Year and Date: 2014-10-24
• [Presentation] ヒトの生理値から集団を科学する (2014)
  • Author(s): 西村貴孝
  • Organizer: 日本生理人類学会第70会大会
  • Place of Presentation: 福岡県福岡市
  • Year and Date: 2014-06-21
  • Invited
• [Presentation] ゲノム多様性情報からヒト集団を科学する。 (2014)
  • Author(s): 中山一大
  • Organizer: 日本生理人類学会第70会大会
  • Place of Presentation: 福岡県福岡市
  • Year and Date: 2014-06-21
  • Invited
• [Presentation] 新規糖尿病感受性遺伝子Ildr2の機能解析 (2014)
  • Author(s): 渡邉和寿、Millings Elizabeth、Fischer Stuart、 Leduc Charles、中山 一大、Leibel Rudolph、岩本 禎彦
  • Organizer: 第68回 日本栄養・食糧学会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2014-05-31
• [Presentation] モンゴル人と東アジア農耕民族の代謝特性の解明を目指したゲノム人類学研究 (2014)
  • Author(s): 中山 一大、大橋 順、Munkhtulga Lkhagvasuren、宮下 洋、岩本 禎彦
  • Organizer: 第68回日本栄養・食糧学会大会 
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2014-05-31
• [Book] つい誰かに教えたくなる人類学63の大疑問 (2015)
  • Author(s): 中山一大、市石博(編) 日本人類学会教育普及委員会（監修）
  • Total Pages: 187
  • Publisher: 講談社