Echocardiographic measures of cardiac target organ damage, including left ventricular mass and relative wall thickness, are powerful predictors of heart disease morbidity and mortality. The aim of this study is to investigate whether single nucleotide polymorphisms in candidate genes for hypertension and heart disease have effects on quantitative measures of hypertensive cardiac target organ damage, independent of their actions on blood pressure levels, in a cohort of hypertensive black sibships. To detect replication of genetic effects across samples, this study took advantage of the affected sibling pair design and created 2 samples, each with 448 unrelated individuals. As part of the Genetic Epidemiology Network of Arteriopathy Study, subjects were screened using 2D echocardiography, and 395 single nucleotide polymorphisms in 80 candidate genes were genotyped. Linear regression was used to test for single nucleotide polymorphisms significantly associated with left ventricular mass index (g/m(2.7)) or relative wall thickness after adjusting for associated covariates. Significant single nucleotide polymorphisms were subsequently tested for consistent directionality in genotype-phenotype relationships across samples. Three single nucleotide polymorphisms, 1 each in the APOE, SCN7A, and SLC20A1 genes, were significantly associated in both samples with left ventricular mass index and had replicate genotype-phenotype relationships. One in the ADRB1 gene was significantly associated with relative wall thickness with replicate effects in both samples. We identified genetic variation that significantly influences left ventricular traits with replicable effects in a cohort of hypertensive, black siblings.