Fine-mapping of disease susceptibility genes by ethnic comparison

• Project/Area Number: 23710228
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical genome science
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: TAKEUCHI Fumihiko 国立感染症研究所, 病原体ゲノム解析研究センター, 室長 (50384152)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ゲノムワイド関連解析 / 国際情報交換 / 英国 / シンガポール / 精密マッピング / 人種差 / 連鎖不平衡 / 国際情報交流

Research Abstract

Genome-wide association studies have successfully identified genetic polymorphisms associated with diseases in numerous chromosomal regions. In this project, we aimed to develop a method to filter the causal variant in the chromosomal region by exploiting ethnic difference.
In the proposed method, we first separated the polymorphisms in a chromosomal region into groups having strong mutual linkage disequilibrium across multiple ethnic groups. Next, we selected representative polymorphisms from each groups, and filtered the group responsible for the disease using multiple regression.
We could narrow down possible causal variants in five regions associated with type 2 diabetes, in 12q24 associated ischemic heart disease and hypertension, and in 13q14 associated with Leprosy and Crohn’s disease. By combining association studies in multiple ethnic groups, we could filter the list of causal variants. By applying to various disease studies, the proposed method would enable earlier functional analysis and drug development.

Research Products

• [Journal Article] Comparing methods for performing trans-ethnic meta-analysis of genome-wide association studies (2013)
  • Author(s): Wang X, Chua HX, Chen P, Ong RT, Sim X, Zhang W, Takeuchi F, Liu X, Khor CC, Tay WT, Cheng CY, Suo C, Liu J, Aung T, Chia KS, Kooner JS, Chambers JC, Wong TY, Tai ES, Kato N, Teo YY
  • Journal Title: Hum. Mol. Genet Volume: 22 Issue: 11 Pages: 2303-2311
  • DOI: 10.1093/hmg/ddt064
  • Peer Reviewed
• [Journal Article] Genome-wide association study of coronary artery disease in the Japanese (2012)
  • Author(s): Fumihiko Takeuchi, Mitsuhiro Yokota, et al.(他23名、3番目)
  • Journal Title: Eur J Hum Genet Volume: 20 Issue: 3 Pages: 333-340
  • DOI: 10.1038/ejhg.2011.184
  • Peer Reviewed
• [Journal Article] Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in East Asians (2011)
  • Author(s): Yamori Y
  • Journal Title: Nat Genetics Volume: 43 Issue: 6 Pages: 531-538
  • DOI: 10.1038/ng.834
  • Peer Reviewed
• [Presentation] T2D-GENES consortium Fine-Mapping of Type 2 Diabetes Susceptibility Loci via Trans-Ethnic Meta-Analysis (2012)
  • Author(s): Horikoshi M, Wiltshire S, Ferreira T, Kato N,Huyghe J, Mahajan A, Takeuchi F, Teo YY, Zeggini E, Morris A, McCarthy M
  • Organizer: 72nd Scientific Sessions of the American Diabetes Associations
  • Place of Presentation: フィラデルフィア(米国)
  • Year and Date: 2012-06-11
• [Presentation] Fine-Mapping of Type 2 Diabetes Susceptibility Loci via Trans-Ethnic Meta-Analysis (2012)
  • Author(s): Momoko Horikoshi
  • Organizer: 72nd Scientific Sessions of the American Diabetes Associations
  • Place of Presentation: フィラデルフィア（米国）
• [Presentation] Trans-ethnic fine-mapping of Type 2 Diabetes susceptibility loci using a "Cosmopolitan" reference panel for imputation (2011)
  • Author(s): Horikoshi M, Wiltshire S, Kato N, Asimit J, Rayner N, Robertson N, Takeuchi F, Mahajan A, Teo YY, Zeggini E, Morris A, McCarthy M
  • Organizer: 61th annual meeting of the American Society of Human Genetics
  • Place of Presentation: モントリオール(カナダ)
  • Year and Date: 2011-10-14
• [Presentation] Fine-mapping of 13q14 locus associated with susceptibility to leprosy and Crohn's disease (2011)
  • Author(s): Takeuchi F
  • Organizer: 61th annual meeting of the American Society of Human Genetics
  • Place of Presentation: モントリオール(カナダ)
  • Year and Date: 2011-10-13
• [Presentation] Fine-mapping of 13q14 locus associated with susceptibility to leprosy and Crohn’s disease (2011)
  • Author(s): Takeuchi, F
  • Organizer: 61th annual meeting of the American Society of Human Genetics
  • Place of Presentation: モントリオール（カナダ）
• [Presentation] Trans-ethnic fine-mapping of Type 2 Diabetes susceptibility loci using a "Cosmopolitan" reference panel for imputation (2011)
  • Author(s): M. Horikoshi, S. Wiltshire, N. Kato, J. Asimit, N. Rayner, N. Robertson, F. Takeuchi, A. Mahajan, T. Yik Ying, E. Zeggini, A. Morris, M. McCarthy
  • Organizer: 61th annual meeting of the American Society of Human Genetics
  • Place of Presentation: モントリオール（カナダ）