Genome-Wide Association Analysis of Plasma B–Type Natriuretic Peptide in Blacks

Background—Numerous experimental studies suggest that B-type natriuretic peptide (BNP) is cardioprotective; however, in clinical studies, higher plasma BNP concentrations have been associated with incident cardiovascular disease and higher left ventricular mass. Genetic association studies may allow us to determine the true causal directions without confounding by compensatory mechanisms. Methods and Results—We performed a meta-analysis of 2 genome-wide association results from a total of 2790 blacks. We assumed an additive genetic model in an association analysis of imputed 2.5 million single-nucleotide polymorphism dosages with residuals generated from multivariable-adjusted logarithmically transformed BNP controlling for relevant covariates and population stratification. Two loci were genome-wide significant, a candidate gene locus NPPB (rs198389, P=1.18×10−09) and a novel missense variant in the KLKB1 locus (rs3733402, P=1.75×10−11) that explained 0.4% and 1.9% of variation in log BNP concentration, r...