Fine-mapping of disease susceptibility genes by ethnic comparison

全基因组关联研究已经成功地确定了与许多染色体区域的疾病相关的遗传多态性。在本项目中，我们旨在开发一种利用种族差异来筛选染色体区域因果变异的方法。在提出的方法中，我们首先将染色体区域的多态性分成在多个种族群体中具有强相互连锁不平衡的组。接下来，我们从每个组中选择具有代表性的多态性，并使用多元回归过滤导致疾病的组。我们可以缩小与2型糖尿病相关的5个区域的可能的因果变异，与缺血性心脏病和高血压相关的12q24区域，与麻风病和克罗恩病相关的13q14区域。通过结合多个族群的关联研究，我们可以过滤因果变异列表。通过应用于各种疾病的研究，所提出的方法将使早期功能分析和药物开发成为可能。

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.