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许多染色体区域中与疾病相关的遗传多态性。在本研究中，我们的目标是开发一种利用种族差异筛选染色体区域中致病变异的方法。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多个种族之间具有强相互连锁不平衡的组。接下来，我们从各组中选择代表性的多态性，并使用多元回归筛选出与疾病相关的组，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。通过结合多个种族群体的关联研究，我们可以过滤因果变异的列表。通过应用于各种疾病的研究，所提出的方法将使早期的功能分析和药物开发。

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.