title: Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium.
abstract: OBJECTIVE
  Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown.
  
  
  RESULTS
  A total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8%) met the diagnostic criteria for OH (systolic/diastolic BP drop ≥ 20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95% confidence interval: 0.90, 0.85-0.96; P = 0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.75-0.95; P = 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.87-0.98; P= 0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.02-1.24; P = 0.02, rs198358: 1.10, 1.01-1.20; P = 0.04, and rs5068: 1.22, 1.04-1.43; P = 0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P= 0.04).
  
  
  CONCLUSIONS
  The overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components.
authors.affiliation: Center for Emergency Medicine, Skåne University Hospital, 205 02 Malmö, Sweden. artur.fedorowski@med.lu.se
authors.forename: Artur
authors.initials: A
authors.lastname: Fedorowski
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Jennifer
authors.initials: J
authors.lastname: Brody
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
authors.forename: Germaine C
authors.initials: GC
authors.lastname: Verwoert
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: David
authors.initials: D
authors.lastname: Couper
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Rice
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Francesco
authors.initials: F
authors.lastname: Mattace-Raso
authors.forename: Andre
authors.initials: A
authors.lastname: Uitterlinden
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Marketa
authors.initials: M
authors.lastname: Sjögren
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Rose
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Witteman
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000235:genetics / Q000503:physiopathology; D001794:Blood Pressure / Q000235:genetics*; D004812:Epidemiologic Methods; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D000959:Antihypertensive Agents