Genetics of African American type 2 diabetes

描述(申请人提供)：非裔美国人患2型糖尿病(T2 DM)的可能性是高加索美国人的两倍，糖尿病并发症的发生率是白人的1.2-5倍。我们已经对来自251个家庭的636对受影响的兄弟姐妹进行了第一次大规模的非裔美国人T2 DM全基因组扫描。我们在染色体6q23-q27上检测到一个连锁峰，位于p端粒的2.08 163.5 cM处。在异质性模型下，这一连锁峰值上升到3.00。该区域为T2 DM和其他人群中相关表型的连锁提供了适度的证据。我们的目标是使用定位克隆方法来识别导致非裔美国人中T2 DM易感性的基因变异。我们将对现有数据进行全面分析，包括对体重指数、确诊年龄、病程、性别的调整，以及使用上位模型和基因组x基因组方法探索相互作用。连锁区域将通过对额外的微卫星进行基因分型来精炼，并启动对有限数量的候选基因的评估。我们将着手构建密集的SNP图谱，以便于识别与非裔美国人T2 DM相关的最小单倍型，然后重点寻找与糖尿病相关的基因。

DESCRIPTION (provided by applicant): African Americans are twice as likely to develop type 2 diabetes (T2DM) as Caucasian Americans, and have 1.2-5 times the rate of diabetic complications. We have carried out the first large-scale genome-wide scan for African American T2DM using 636 affected sibling pairs from 251 families. We detected a linkage peak on chromosome 6q23-q27, LOD 2.08 163.5cM from the p telomere. Under models of heterogeneity, this linkage peak rises to 3.00. This region has provided modest evidence for linkage to T2DM and related phenotypes in other populations. Our goal is to use a positional cloning approach to identify variants in genes that contribute to T2DM susceptibility in the African American population. We will conduct comprehensive analyses of existing data, including adjustments for BMI, age at diagnosis, duration of disease, gender, and exploration of interactions using epistasis models and a genome x genome approach. The region of linkage will be refined by genotyping additional microsatellites, and an evaluation of a limited number of candidate genes initiated. We will embark upon construction of a dense SNP map to facilitate the identification of minimal haplotypes associated with African American T2DM, followed by a focused search for genes contributing to diabetes.