title: Genome-wide association analysis of plasma B-type natriuretic peptide in blacks: the Jackson Heart Study.
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.
  
  
  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).
  
  
  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.
authors.forename: Solomon K
authors.initials: SK
authors.lastname: Musani
authors.forename: Ervin R
authors.initials: ER
authors.lastname: Fox
authors.forename: Aldi
authors.initials: A
authors.lastname: Kraja
authors.forename: Aurelian
authors.initials: A
authors.lastname: Bidulescu
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Honghuang
authors.initials: H
authors.lastname: Lin
authors.forename: Ashley
authors.initials: A
authors.lastname: Beecham
authors.forename: Ming-Huei
authors.initials: MH
authors.lastname: Chen
authors.forename: Janine F
authors.initials: JF
authors.lastname: Felix
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
authors.forename: Sharon L R
authors.initials: SL
authors.lastname: Kardia
authors.forename: Ching-Ti
authors.initials: CT
authors.lastname: Liu
authors.forename: Mike A
authors.initials: MA
authors.lastname: Nalls
authors.forename: Tatjana
authors.initials: T
authors.lastname: Rundek
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.forename: Jennifer
authors.initials: J
authors.lastname: Smith
authors.forename: Yan V
authors.initials: YV
authors.lastname: Sun
authors.forename: Gregory
authors.initials: G
authors.lastname: Wilson
authors.forename: Zhaogong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.forename: Herman A
authors.initials: HA
authors.lastname: Taylor
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000450:Aldosterone / Q000097:blood / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000208:ethnology / Q000235:genetics; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D008922:Mississippi; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012083:Renin / Q000097:blood / Q000235:genetics
chemical_list: D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D012083:Renin
keywords: genetic association studies; genetics; genome-wide association study; genotype