Aortic root dilatation is a major pathophysiological mechanism for aortic regurgitation and predisposes the aortic root to dissection or rupture. However, only a small proportion of the variance of aortic root size can be explained by its known clinical and demographic correlates. The present study was undertaken to determine the heritability of echocardiographically derived aortic root diameter in the American Indian participants in the second Strong Heart Study examination. Echocardiograms were analyzed in 1373 SHS participants who had > or =1 family member in the cohort. Heritability calculations were performed by using variance component analysis as implemented in SOLAR, a computer analysis program. In a polygenic model, the variables entered and identified as covariates of larger aortic root diameter were older age, male sex, and center (P<0.001), which accounted for 35% of the overall variability of aortic root diameter. After simultaneous adjustment was made for these significant covariates, the proportion of phenotypic variance due to additive genetic contribution or residual heritability (h2) was 0.51 (SE=0.08, P<0.001). Additionally, simultaneous adjustment for height, weight, and systolic and diastolic BPs yielded slightly lower residual h2 of aortic root diameter (h2=0.44, SE=0.08, P<0.001), which accounted for 26% of the overall variance of aortic root size. Because center effects were identified as significant covariates in the analyses, h2 analyses were performed separately in Arizona, Oklahoma, and North/South Dakota centers, which confirmed that a significant proportion of the phenotypic variance of aortic root diameter is due to additive genetic contribution. Heredity explains a substantial proportion of the variability of aortic root size that is not accounted for by age, sex, body size, and blood pressure. Echocardiographic screening of family members with aortic root dilatation may identify other individuals predisposed to aortic dissection or rupture.