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. Hirschhorn; Olle Melander; Thomas J. Wang

doi:10.1038/ng.328

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 journal › Article › peer-review

344 Scopus citations

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 × 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 language	English (US)
Pages (from-to)	348-353
Number of pages	6
Journal	Nature genetics
Volume	41
Issue number	3
DOIs	https://doi.org/10.1038/ng.328
State	Published - Mar 2009
Externally published	Yes

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/ng.328

Cite this

Newton-Cheh, C., Larson, M. G., Vasan, R. S., Levy, D., Bloch, K. D., Surti, A., Guiducci, C., Kathiresan, S., Benjamin, E. J., Struck, J., Morgenthaler, N. G., Bergmann, A., Blankenberg, S., Kee, F., Nilsson, P., Yin, X., Peltonen, L., Vartiainen, E., Salomaa, V., ... Wang, T. J. (2009). Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure. Nature genetics, 41(3), 348-353. https://doi.org/10.1038/ng.328

Newton-Cheh, C, Larson, MG, Vasan, RS, Levy, D, Bloch, KD, Surti, A, Guiducci, C, Kathiresan, S, Benjamin, EJ, Struck, J, Morgenthaler, NG, Bergmann, A, Blankenberg, S, Kee, F, Nilsson, P, Yin, X, Peltonen, L, Vartiainen, E, Salomaa, V, Hirschhorn, JN, Melander, O & Wang, TJ 2009, 'Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure', Nature genetics, vol. 41, no. 3, pp. 348-353. https://doi.org/10.1038/ng.328

@article{e1682d7463b8497d930e131e23fd83fa,

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 × 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.",

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

note = "Funding Information: The Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine was supported by contract no. N01-HC-25195 and the CardioGenomics Program for Genomic Applications (HL66582). The ANP measurements in Finrisk97 were performed by the MORGAM Biomarkers Study funded by the Medical Research Council, UK (G0601463: 80983). C.N.-C. was supported by NIH K23-HL-080025, a Doris Duke Charitable Foundation Clinical Scientist Development Award and a Burroughs Wellcome Fund Career Award for Medical Scientists. T.J.W. was supported by NIH K23-HL-074077, R01-HL-086875, R01-HL-083197, R01-DK-081572 and the American Heart Association. R.S.V. was supported by a research career award from the NIH (K24-HL-04334, R01 HL093328). K.D.B. was supported by R01-HL-070896. L.P. was supported by the Center of Excellence in Complex Disease Genetics of the Academy of Finland, Biocentrum Helsinki Foundation, Finland and the Nordic Center of Excellence. V.S. was supported by the Sigrid Juselius Foundation. P.N. was supported by the Ernhold Lundstrom Foundation and the Swedish Heart and Lung Foundation. O.M. was supported by the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Medical Faculty of Lund University, Malm{\"o} University Hospital, the Albert P{\aa}hlsson Research Foundation, the Crafoord foundation, the Ernhold Lundstr{\"o}ms Research Foundation, the Region Skane, the Hulda and Conrad Mossfelt Foundation, the King Gustaf V and Queen Victoria Foundation and the Lennart Hanssons Memorial Fund. The authors also wish to thank the following companies for their support of the natriuretic peptide assays: Shionogi, BRAHMS, and Siemens Healthcare Diagnostics. C.N.-C., O.M. and T.J.W. had full access to the study data and take responsibility for its content. The funding sources had no role in the design, analysis and interpretation, the writing of the manuscript or the decision to submit for publication.",

year = "2009",

month = mar,

doi = "10.1038/ng.328",

language = "English (US)",

volume = "41",

pages = "348--353",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "3",

}

TY - JOUR

T1 - Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure

AU - Newton-Cheh, Christopher

AU - Larson, Martin G.

AU - Vasan, Ramachandran S.

AU - Levy, Daniel

AU - Bloch, Kenneth D.

AU - Surti, Aarti

AU - Guiducci, Candace

AU - Kathiresan, Sekar

AU - Benjamin, Emelia J.

AU - Struck, Joachim

AU - Morgenthaler, Nils G.

AU - Bergmann, Andreas

AU - Blankenberg, Stefan

AU - Kee, Frank

AU - Nilsson, Peter

AU - Yin, Xiaoyan

AU - Peltonen, Leena

AU - Vartiainen, Erkki

AU - Salomaa, Veikko

AU - Hirschhorn, Joel N.

AU - Melander, Olle

AU - Wang, Thomas J.

N1 - Funding Information: The Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine was supported by contract no. N01-HC-25195 and the CardioGenomics Program for Genomic Applications (HL66582). The ANP measurements in Finrisk97 were performed by the MORGAM Biomarkers Study funded by the Medical Research Council, UK (G0601463: 80983). C.N.-C. was supported by NIH K23-HL-080025, a Doris Duke Charitable Foundation Clinical Scientist Development Award and a Burroughs Wellcome Fund Career Award for Medical Scientists. T.J.W. was supported by NIH K23-HL-074077, R01-HL-086875, R01-HL-083197, R01-DK-081572 and the American Heart Association. R.S.V. was supported by a research career award from the NIH (K24-HL-04334, R01 HL093328). K.D.B. was supported by R01-HL-070896. L.P. was supported by the Center of Excellence in Complex Disease Genetics of the Academy of Finland, Biocentrum Helsinki Foundation, Finland and the Nordic Center of Excellence. V.S. was supported by the Sigrid Juselius Foundation. P.N. was supported by the Ernhold Lundstrom Foundation and the Swedish Heart and Lung Foundation. O.M. was supported by the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Medical Faculty of Lund University, Malmö University Hospital, the Albert Påhlsson Research Foundation, the Crafoord foundation, the Ernhold Lundströms Research Foundation, the Region Skane, the Hulda and Conrad Mossfelt Foundation, the King Gustaf V and Queen Victoria Foundation and the Lennart Hanssons Memorial Fund. The authors also wish to thank the following companies for their support of the natriuretic peptide assays: Shionogi, BRAHMS, and Siemens Healthcare Diagnostics. C.N.-C., O.M. and T.J.W. had full access to the study data and take responsibility for its content. The funding sources had no role in the design, analysis and interpretation, the writing of the manuscript or the decision to submit for publication.

PY - 2009/3

Y1 - 2009/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=61349089775&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61349089775&partnerID=8YFLogxK

U2 - 10.1038/ng.328

DO - 10.1038/ng.328

M3 - Article

C2 - 19219041

AN - SCOPUS:61349089775

SN - 1061-4036

VL - 41

SP - 348

EP - 353

JO - Nature genetics

JF - Nature genetics

IS - 3

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this