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

Christopher Newton-Cheh, Martin G. Larson, Ramachandran S. Vasan, Daniel Levy, Kenneth D. Bloch, Aarti Surti, Candace Guiducci, Sekar Kathiresan, Emelia J. Benjamin, Joachim Struck, Nils G. Morgenthaler, Andreas Bergmann, Stefan Blankenberg, Frank Kee, Peter Nilsson, Xiaoyan Yin, Leena Peltonen, Erkki Vartiainen, Veikko Salomaa, Joel N. HirschhornOlle Melander, Thomas J. Wang

Research output: Contribution to journalArticlepeer-review

345 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)348-353
Number of pages6
JournalNature Genetics
Issue number3
StatePublished - Mar 2009
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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