Association of Common Variants in NPPA and NPPB with Circulating Natriuretic Peptides and Blood Pressure

Blood pressure is a heritable trait, but no common genetic variants contributing to blood pressure in humans have been definitively established. Natriuretic peptides (NP) have blood pressure-lowering properties. Genotyping SNPs at the NPPA/NPPB locus in 14,743 individuals of European ancestry identified associations of plasma atrial natriuretic peptide with rs5068 (P=8×10(−70)), rs198358 (P=8×10(−30)), and rs632793 (P=2×10(−10)), and of plasma B-type natriuretic peptide with rs5068 (P=3×10(−12)), rs198358 (P=1×10(−25)), and rs632793 (P=2×10(−68)). In 29,717 individuals, the alleles of rs5068 and rs198358 related to increased circulating NP concentrations were associated with lower systolic (P=2×10(−6) and 6×10(−5), respectively) and diastolic blood pressure (P=1×10(−6) and 5×10(−5)), and reduced odds of hypertension (odds ratio 0.85, 95% confidence interval, 0.79–0.92, P=4×10(−5); odds ratio 0.90, 95% confidence interval, 0.85–0.95, P=2×10(−4), respectively). Common genetic variants related to circulating NP concentrations contribute to inter-individual variation in blood pressure and hypertension.