The EBF1 locus variant rs11953630 was significantly associated with orthostatic hypotension (OR 0.90; 95% CI 0.85-0.96; P=0.001), but overall association between BP loci and OH was weak.
Meta-Analysis (n=38,970)
Yes
Are recently discovered blood pressure-associated gene variants associated with orthostatic hypotension in individuals of European ancestry?
Common gene variants associated with resting blood pressure have weak and inconsistent associations with orthostatic hypotension, suggesting they share few genetic components.
Effect estimate: OR 0.90 (95% CI 0.85-0.96)
p-value: p=0.001
AIMS: 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. METHODS AND 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). CONCLUSION: 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.
Fedorowski et al. (Sat,) conducted a meta-analysis in Orthostatic hypotension (n=38,970). Blood pressure-associated single nucleotide polymorphisms (SNPs) vs. Major allele was evaluated on Orthostatic hypotension (OR 0.90, 95% CI 0.85-0.96, p=0.001). The EBF1 locus variant rs11953630 was significantly associated with orthostatic hypotension (OR 0.90; 95% CI 0.85-0.96; P=0.001), but overall association between BP loci and OH was weak.