Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Compared to other common complex diseases, it has proved remarkably difficult to establish the genetic basis of blood-pressure elevation. A multi-stage genome-wide association study involving 200,000 individuals of European descent provides some of the missing detail in the genetic picture. The study identified 16 relevant loci, of which only 6 contain genes previously known or suspected to regulate blood pressure. An association was found between hypertension, the thickness of the left ventricular wall, stroke and coronary artery disease, but not kidney disease or kidney function. Comparison with data from more than 75,000 people of East Asian, South Asian and African ancestries confirmed that many of the variants identified in European-ancestry subjects also influence blood pressure in other populations. Blood pressure is a heritable trait1 influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure)2. Even small increments in blood pressure are associated with an increased risk of cardiovascular events3. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3–GUCY1B3, NPR3–C5orf23, ADM, FURIN–FES, GOSR2, GNAS–EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.