Fine-mapping of disease susceptibility genes by ethnic comparison

通过种族比较精细绘制疾病易感基因

• 批准号: 23710228
• 负责人: TAKEUCHI Fumihiko
• 金额: $ 2.91万
• 依托单位: National Institute of Infectious Diseases
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23710228/
• 关键词: 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

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.

全基因组关联研究已成功鉴定出与许多染色体区域疾病相关的遗传多态性。在这个项目中，我们的目标是开发一种利用种族差异来过滤染色体区域中因果变异的方法。在所提出的方法中，我们首先将染色体区域中的多态性分成跨多个种族群体之间具有强相互连锁不平衡的组。接下来，我们从每组中选择了代表性多态性，并使用多元回归过滤了导致该疾病的组。我们可以缩小与 2 型糖尿病相关的 5 个区域、与缺血性心脏病和高血压相关的 12q24 区域以及与麻风病和克罗恩病相关的 13q14 区域中可能的因果变异的范围。通过结合多个种族的关联研究，我们可以过滤因果变异列表。通过应用于各种疾病研究，所提出的方法将能够实现早期功能分析和药物开发。

项目成果

Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians.

全基因组关联研究的荟萃分析确定了与东亚人血压变化相关的常见变异。

• DOI: 10.1038/ng.834
• 发表时间: 2011-06
• 期刊: Nature genetics
• 影响因子: 30.8

Trans-ethnic fine-mapping of Type 2 Diabetes susceptibility loci using a "Cosmopolitan" reference panel for imputation

使用“Cosmopolitan”参考面板进行插补，对 2 型糖尿病易感性位点进行跨种族精细绘图

• 发表时间: 2011
• 作者: Horikoshi M;Wiltshire S;Kato N;Asimit J;Rayner N;Robertson N;Takeuchi F;Mahajan A;Teo YY;Zeggini E;Morris A;McCarthy M
• 通讯作者: McCarthy M

Genome-wide association study of coronary artery disease in the Japanese

• DOI: 10.1038/ejhg.2011.184
• 发表时间: 2012-03-01
• 期刊: EUROPEAN JOURNAL OF HUMAN GENETICS
• 影响因子: 5.2
• 作者: Takeuchi, Fumihiko;Yokota, Mitsuhiro;Kato, Norihiro
• 通讯作者: Kato, Norihiro

Comparing methods for performing trans-ethnic meta-analysis of genome-wide association studies

• DOI: 10.1093/hmg/ddt064
• 发表时间: 2013-06-01
• 期刊: HUMAN MOLECULAR GENETICS
• 影响因子: 3.5
• 作者: Wang, Xu;Chua, Hui-Xiang;Teo, Yik-Ying
• 通讯作者: Teo, Yik-Ying

T2D-GENES consortium Fine-Mapping of Type 2 Diabetes Susceptibility Loci via Trans-Ethnic Meta-Analysis

T2D-GENES 联盟通过跨种族荟萃分析精细绘制 2 型糖尿病易感性位点

• 发表时间: 2012
• 作者: Horikoshi M;Wiltshire S;Ferreira T;Kato N,Huyghe J;Mahajan A;Takeuchi F;Teo YY;Zeggini E;Morris A;McCarthy M
• 通讯作者: McCarthy M