Genetics of African American type 2 diabetes

描述（由申请人提供）：非裔美国人患2型糖尿病（T2 DM）的可能性是白人美国人的两倍，糖尿病并发症的发生率是白人美国人的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第一次大规模的非裔美国人T2 DM全基因组扫描。 在染色体6 q23-q27上检测到一个连锁峰，其LOD为2.08 ~ 163.5cM。在异质性模型下，这个连锁峰值上升到3.00。该区域提供了与其他人群中的T2 DM和相关表型相关的适度证据。我们的目标是使用定位克隆的方法，以确定基因的变异，有助于T2 DM的易感性在非洲裔美国人的人口。我们将对现有数据进行全面分析，包括调整BMI，诊断时的年龄，疾病持续时间，性别，以及使用上位性模型和基因组x基因组方法探索相互作用。将通过对额外的微卫星进行基因分型，并对有限数量的候选基因进行评价，来细化连锁区域。我们将着手构建一个密集的SNP图谱，以促进与非洲裔美国人T2 DM相关的最小单倍型的鉴定，然后重点寻找导致糖尿病的基因。

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.