2 research outputs found
Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk
Elevated blood pressure is the leading heritable risk factor for cardiovascular disease
worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse
pressure) among UK Biobank participants of European ancestry with independent replication
in other cohorts, leading to discovery and validation of 107 novel loci. We also identify new
independent variants at 11 previously reported blood pressure loci. Combined with results
from a range of in-silico functional analyses and wet bench experiments, our findings highlight
new biological pathways for blood pressure regulation enriched for genes expressed in
vascular tissues and identify potential therapeutic targets for hypertension. Results from
genetic risk score models raise the possibility of a precision medicine approach through early
lifestyle intervention to offset the impact of blood pressure raising variants on future
cardiovascular disease risk
Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention