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High blood pressure remains the major heritable and modifiable risk factor for cardiovascular disease (CVD). Persistent high blood pressure, or hypertension, is a complex trait with both genetic and environmental interactions. Despite swift advances in genomics, translating new discoveries to further our understanding of the underlying molecular mechanisms remains a challenge. More than 500 loci implicated in the regulation of blood pressure (BP) have been revealed by genome-wide association studies (GWAS) in 2018 alone, taking the total number of BP genetic loci to over 1,000. Even with the large number of loci now associated to BP, the genetic variance explained by all loci together remains low (~5.7%). These genetic associations have elucidated mechanisms and pathways regulating BP, highlighting potential new therapeutic and drug repurposing targets. A large proportion of the BP loci were discovered and reported simultaneously by multiple research groups, creating a knowledge gap, where the reported loci to date have not been investigated in a harmonious way. Here, we review the BP-associated genetic variants reported across GWAS studies and investigate their potential impact on the biological systems using in silico enrichment analyses for pathways, tissues, gene ontology and genetic pleiotropy.
This article was published in the following journal.
Name: Human molecular genetics
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Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.
A technique for identifying individuals of a species that is based on the uniqueness of their DNA sequence. Uniqueness is determined by identifying which combination of allelic variations occur in the individual at a statistically relevant number of different loci. In forensic studies, RESTRICTION FRAGMENT LENGTH POLYMORPHISM of multiple, highly polymorphic VNTR LOCI or MICROSATELLITE REPEAT loci are analyzed. The number of loci used for the profile depends on the ALLELE FREQUENCY in the population.
Method in which repeated blood pressure readings are made while the patient undergoes normal daily activities. It allows quantitative analysis of the high blood pressure load over time, can help distinguish between types of HYPERTENSION, and can assess the effectiveness of antihypertensive therapy.
A response by the BARORECEPTORS to increased BLOOD PRESSURE. Increased pressure stretches BLOOD VESSELS which activates the baroreceptors in the vessel walls. The net response of the CENTRAL NERVOUS SYSTEM is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral VASCULAR RESISTANCE and by lowering CARDIAC OUTPUT. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure.
PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.
Cardiovascular disease (CVD)
Acute Coronary Syndromes (ACS) Blood Cardiovascular Dialysis Hypertension Stent Stroke Vascular Cardiovascular disease (CVD) includes all the diseases of the heart and circulation including coronary heart disease (angina...