Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure

We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and 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 that showed association with increased circulating natriuretic peptide concentrations were also found to be 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), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 × 10^-5; OR = 0.90, 95% CI = 0.85-0.95, P = 2 × 10^-4, respectively). Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension.