Genetics of Chronic Kidney Disease

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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 1000African-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-Americansibling pairs.