title: Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure.
abstract: 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 x 10(-70)), rs198358 (P = 8 x 10(-30)) and rs632793 (P = 2 x 10(-10)), and of plasma B-type natriuretic peptide with rs5068 (P = 3 x 10(-12)), rs198358 (P = 1 x 10(-25)) and rs632793 (P = 2 x 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 x 10(-6) and 6 x 10(-5), respectively) and diastolic blood pressure (P = 1 x 10(-6) and 5 x 10(-5)), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 x 10(-5); OR = 0.90, 95% CI = 0.85-0.95, P = 2 x 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.
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA. cnewtoncheh@chgr.mgh.harvard.edu
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Aarti
authors.initials: A
authors.lastname: Surti
authors.forename: Candace
authors.initials: C
authors.lastname: Guiducci
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.forename: Nils G
authors.initials: NG
authors.lastname: Morgenthaler
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.forename: Frank
authors.initials: F
authors.lastname: Kee
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yin
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Erkki
authors.initials: E
authors.lastname: Vartiainen
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000235:genetics*; D045265:Natriuretic Peptides / Q000097:blood*; D020641:Polymorphism, Single Nucleotide
chemical_list: C472955:NPPA protein, human; D045265:Natriuretic Peptides; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor