Genetics of Chronic Kidney Disease

描述（由申请人提供）：慢性肾脏疾病（CKD）折磨着11%的美国成年人。CKD的易感性差异很大，提示遗传因素的作用。了解CKD的遗传预测因素可能会导致更好的方法来识别和治疗有风险的个体，以防止终末期肾脏疾病的发病率和患病率上升。动脉病变遗传流行病学网络（GENOA）进行了全基因组连锁和关联研究，以确定影响血压和高血压的动脉硬化性脑、心脏和外周血管并发症的基因。拟议的研究将通过确定具有2个或更多高血压成员的欧洲白人和非洲裔美国兄弟姐妹中CKD的遗传预测因子来扩展这些努力。我们建议在这些不同种族的高风险人群中确定CKD的遗传预测因子，实现以下具体目标：目的1：确定1000名欧洲白人和1000名非裔美国兄弟姐妹中动脉硬化的传统或新的危险因素（已经通过GENOA测量）是否能预测肾小球滤过率或蛋白尿。目的2：确定高血压或其动脉硬化性脑、心脏和周围血管并发症（已由GENOA测量）的bbbb250候选基因的双等位基因多态性是否能预测1000名欧洲白人和1000名非裔美国兄弟姐妹的肾小球滤过率或蛋白尿。目的3：确定跨越基因组的387个高度多态性串联重复标记位点（已经由GENOA测量）是否与影响1000多对欧洲白人和1000多对非裔美国人兄弟姐妹肾小球滤过率或蛋白尿的基因相关。

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) afflicts 11% of the adult US population. Susceptibility to CKD varies considerably, suggesting a role for genetic factors. Knowledge of genetic predictors of CKD may lead to better methods of identifying and treating individuals at risk to prevent the rising incidence and prevalence of endstage renal disease. The Genetic Epidemiology Network of Arteriopathy (GENOA) has conducted genomewide linkage and association studies to identify genes influencing blood pressure and the arteriosclerotic cerebral, cardiac, and peripheral vascular complications of hypertension. The proposed investigation will extend those efforts by identifying genetic predictors of CKD in previously well-characterized European-white and African- American sibships with 2 or more hypertensive members. We propose to identify genetic predictors of CKD in these ethnically diverse, high-risk cohorts by accomplishing the following specific aims: Aim 1: Determine whether conventional or novel risk factors for arteriosclerosis (already measured by GENOA) predict glomerular filtration rate or albuminuria in 1000 European-white and 1000 African-American siblings. Aim 2: Determine whether diallelic polymorphisms in >250 candidate genes for hypertension or its arteriosclerotic cerebral, cardiac, and peripheral vascular vascular complications (already measured by GENOA) predict glomerular filtration rate or albuminuria in 1000 European-white and 1000 African-American siblings. Aim 3: Determine whether any of 387 highly polymorphic tandem repeat marker loci spanning the genome (already measured by GENOA) are linked to genes influencing glomerular filtration rate or albuminuria in more than 1000 European-white and 1000 African-American sibling pairs.