Genetics of Chronic Kidney Disease

描述（由申请人提供）：慢性肾脏疾病（CKD）困扰着11%的美国成年人口。CKD的易感性差异很大，表明遗传因素的作用。CKD的遗传预测因子的知识可能会导致更好的方法来识别和治疗个体的风险，以防止终末期肾病的发病率和患病率的上升。动脉病遗传流行病学网络（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脑、心脏和外周血管并发症的基因。这项研究将通过在先前特征良好的有2个或更多高血压成员的欧洲白人和非洲裔美国人同胞中鉴定CKD的遗传预测因子来扩展这些努力。我们建议通过实现以下特定目标来确定这些种族多样的高风险队列中CKD的遗传预测因子：目标1：确定1000名欧洲白人和1000名非洲裔美国人兄弟姐妹中动脉硬化的传统或新风险因素（已通过GENOA测量）是否可预测肾小球滤过率或蛋白尿。目标二：在1000名欧洲白人和1000名非洲裔美国同胞中，确定高血压或其动脉脑、心脏和外周血管并发症（已通过GENOA测量）的>250个候选基因中的双等位基因多态性是否可预测肾小球滤过率或蛋白尿。目标3：确定是否有任何387个高度多态性的串联重复标记基因座跨越基因组（已测量的基因）与影响肾小球滤过率或蛋白尿的基因在1000多个欧洲白人和1000个非洲裔美国人的同胞对。

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.