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Genome-wide association analysis of plasma B-type natriuretic peptide in blacks: the Jackson Heart Study.
- Source :
-
Circulation. Cardiovascular genetics [Circ Cardiovasc Genet] 2015 Feb; Vol. 8 (1), pp. 122-30. Date of Electronic Publication: 2015 Jan 05. - Publication Year :
- 2015
-
Abstract
- Background: Numerous experimental studies suggest that B-type natriuretic peptide (BNP) is cardioprotective; however, in clinical studies, higher plasma BNP concentrations have been associated with incident cardiovascular disease and higher left ventricular mass. Genetic association studies may allow us to determine the true causal directions without confounding by compensatory mechanisms.<br />Methods and Results: We performed a meta-analysis of 2 genome-wide association results from a total of 2790 blacks. We assumed an additive genetic model in an association analysis of imputed 2.5 million single-nucleotide polymorphism dosages with residuals generated from multivariable-adjusted logarithmically transformed BNP controlling for relevant covariates and population stratification. Two loci were genome-wide significant, a candidate gene locus NPPB (rs198389, P=1.18×10(-09)) and a novel missense variant in the KLKB1 locus (rs3733402, P=1.75×10(-11)) that explained 0.4% and 1.9% of variation in log BNP concentration, respectively. The observed increase in BNP concentration was proportional to the number of effect allele copies, and an average of 8.1 pg/mL increase was associated with 2 allele copies. In a companion study, single-nucleotide polymorphisms in this loci were cross-checked with genome-wide association results for the aldosterone/renin ratio in individuals of European ancestry, and rs3733402 was genome-wide significant (P<5.0×10(-8)), suggesting possible shared genetic architecture for these 2 pathways. Other statistically significant relations for these single-nucleotide polymorphisms included the following: rs198389 with systolic blood pressure in blacks (COGENT consortium) and rs198389 and rs3733402 with left ventricular mass in whites (EchoGEN consortium).<br />Conclusions: These findings improve our knowledge of the genetic basis of BNP variation in blacks, demonstrate a possible shared allelic architecture for BNP with aldosterone-renin ratio, and motivate further studies of underlying mechanisms.<br /> (© 2015 American Heart Association, Inc.)
- Subjects :
- Adult
Aged
Aldosterone blood
Aldosterone genetics
Female
Humans
Male
Middle Aged
Mississippi
Renin blood
Renin genetics
Black or African American genetics
Cardiovascular Diseases blood
Cardiovascular Diseases ethnology
Cardiovascular Diseases genetics
Genetic Loci
Genome-Wide Association Study
Natriuretic Peptide, Brain blood
Natriuretic Peptide, Brain genetics
Polymorphism, Single Nucleotide
Subjects
Details
- Language :
- English
- ISSN :
- 1942-3268
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Circulation. Cardiovascular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 25561047
- Full Text :
- https://doi.org/10.1161/CIRCGENETICS.114.000900