Genetics of African American type 2 diabetes

描述（由申请人提供）：非洲裔美国人患2型糖尿病（T2DM）的可能性是白人的两倍，糖尿病并发症的发生率是白人的1.2-5倍。我们对来自251个家庭的636对受影响的兄弟姐妹进行了非裔美国人T2DM的首次大规模全基因组扫描。在距p端粒2.08 163.5cM的6q23-q27染色体上检测到一个连锁峰。在异质性模型下，这一联系峰值上升到3.00。该地区与其他人群的T2DM和相关表型有一定的联系。我们的目标是使用定位克隆方法来鉴定非裔美国人中导致2型糖尿病易感性的基因变异。我们将对现有数据进行全面分析，包括调整BMI、诊断年龄、疾病持续时间、性别，并利用上位模型和基因组x基因组方法探索相互作用。将通过增加微卫星的基因分型和开始对有限数量的候选基因进行评价来完善连锁区域。我们将着手构建密集的SNP图谱，以促进与非裔美国人2型糖尿病相关的最小单倍型的鉴定，然后重点寻找与糖尿病有关的基因。

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.