Development of new risk model for predicting type 2 diabetes mellitus combining genetic profiles (single nucleotide polymorphisms) and classical diabetes risk factors

• Project/Area Number: 26870208
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics; Epidemiology and preventive medicine
• Research Institution: Niigata University
• Principal Investigator: Kodama Satoru 新潟大学, 医歯学総合研究科, 助教 (50638781)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ゲノムワイド研究 / 糖尿病感受性遺伝子 / 危険遺伝子 / メタ解析 / 糖尿病 / GWAS / risk allele / SNP / 2型糖尿病 / メタ分析 / 全ゲノム関連解析 / 一塩基多型 / 対立遺伝子 / 量―反応関係

Outline of Final Research Achievements

Our meta-analyses which aimed to assess the ability of genetic testing for type 2　diabetes mellitus succeeded in establishing the following quantitative evidence. In conclusion, using only diabetes-susceptible genes would be almost impossible to detect individuals at high risk of diabetes. (1) The dose-response curve between cumulative risk alleles (RAs) and risk of diabetes indicated that the increase in the diabetes risk in relation to cumulative RAs was weakened as the number of RAs carried increased. (2) Diagnostic value of genetic testing based on GWAS was considered minimal, which was concluded from pooled positive likelihood ratio and negative likelihood ratio was 1.32 and 0.76, respectively. (3) Pooled OR of incident diabetes for carrying one RA was 1.10, which approximately corresponded to one for the increase in body weight by 2 kg.

Research Products

• [Journal Article] Quantitative relationship between cumulative risk alleles based on genome-wide association studies and type 2 diabetes mellitus: a systematic review and meta-analysis. (2017)
  • Author(s): Kodama S, Fujihara K, Ishiguro H, Horikawa C, Ohara N, Yachi Y, Tanaka S, Shimano H, Kato K, Hanyu O, Sone H.
  • Journal Title: J Epidemiol. Volume: in press
  • NAID: 130006301960
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Unstable body weight and incident type 2 diabetes mellitus - A meta-analysis (in press) (2017)
  • Author(s): Kodama S, Fujihara K, Ishiguro H, Horikawa C, Ohara N, Yachi Y, Tanaka S, Shimano H, Kato K, Hanyu O, Sone H
  • Journal Title: Journal of diabetes investigation Volume: - Issue: 4 Pages: 501-509
  • DOI: 10.1111/jdi.12623
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Quantitative assessment of genetic testing for type 2 diabetes mellitus based on findings of genome-wide association studies (2016)
  • Author(s): Kodama S, Fujihara K, Ishiguro H, Horikawa C, Ohara N, Yachi Y, Tanaka S, Shimano H, Kato K, Hanyu O, Sone H
  • Journal Title: Am J Surg Pathol Volume: 11 Issue: 11 Pages: 816-818
  • DOI: 10.1016/j.annepidem.2016.09.004
  • Peer Reviewed / Open Access
• [Journal Article] Meta-analytic research on the relationship between cumulative risk alleles and risk of type 2 diabetes mellitus (2016)
  • Author(s): Kodama S, Fujihara K, Ishiguro H, Horikawa C, Ohara N, Yachi Y, Tanaka S, Shimano H, Kato K, Hanyu O, Sone H
  • Journal Title: Diabetes/metabolism research and reviews Volume: 32 Issue: 2 Pages: 178-186
  • DOI: 10.1002/dmrr.2680
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 体重変動と2型糖尿病発症との関連性に関するメタ解析 (2015)
  • Author(s): 児玉 暁, 羽入 修, 加藤 公則, 曽根 博仁
  • Organizer: 第36回日本肥満学会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-02
• [Presentation] ゲノムワイド関連解析（GWAS）で検出された一塩基多型（SNP）を用いた2型糖尿病のスクリーニング・予測能の定量メタ分析 (2015)
  • Author(s): 児玉 暁, 藤原 和哉, 小原 伸雅, 加藤 公則, 羽入 修, 曽根 博仁
  • Organizer: 第112回日本内科学会
  • Place of Presentation: みやこめっせ（京都府・京都市）
  • Year and Date: 2015-04-10
• [Presentation] Predictive Value of Combined Single Nucleotide Polymorphisms for Diabetes Mellitus - A Meta-analysis Author Block: SATORU KODAMA, CHIKA HORIKAWA, SATOSHI MATSUNAGA, KAZUYA FUJIHARA, YORIKO HEIANZA, AYUMI HIROSE, TAKAHO YAMADA, AKIKO SUZUKI, OSAMU HANYU, HIROHITO SONE, Niigata, Japan, Mito, Ibaraki, Japan (2014)
  • Author(s): SATORU KODAMA, CHIKA HORIKAWA, SATOSHI MATSUNAGA, KAZUYA FUJIHARA, YORIKO HEIANZA, AYUMI HIROSE, TAKAHO YAMADA, AKIKO SUZUKI, OSAMU HANYU, HIROHITO SONE
  • Organizer: 第74回アメリカ糖尿病学会
  • Place of Presentation: Moscone Center in San Francisco (USA)
  • Year and Date: 2014-06-15
• [Presentation] ゲノムワイド関連解析（GWAS）における糖尿病関連遺伝子と定量的糖尿病相関性のメタ分析 (2014)
  • Author(s): 児玉暁，藤原和哉，松永佐澄志，古川和郎，山田貴穂 ，鈴木亜希子，島野仁 ，羽入修，曽根博仁
  • Organizer: 第111回日本内科学会
  • Place of Presentation: 東京国際フォーラム(東京）
  • Year and Date: 2014-04-11
• [Book] Diabetes Frontier (2016)
  • Author(s): 児玉暁，曽根博仁
  • Total Pages: 6
  • Publisher: メディカルレビュー社