Genetic Variants in Novel Pathways Influence Blood Pressure and Cardiovascular Disease Risk
By George B. Ehret, Georg Benedikt. Nature, 2011
2,062 citations recorded by the source corpus.
Blood pressure is a heritable trait 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). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. 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.
Subfields: Cardiology and Cardiovascular Medicine, Endocrinology, Diabetes and Metabolism, Genetics
View Paper: https://www.semanticscholar.org/paper/bfb0926e63511683058d6c1561dd0942b3a1a46a
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Citations in the corpus
- Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data (2013, background): “Other assessments, such as addressing population stratification by the evaluation of genetic principal components, or testing for the attenuation of genetic associations with the outcome on adjustment for the risk factor [Glymour et al., 2012], require individual-level data.”
- Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression (2015, background): “Causal effect of blood pressure on coronary artery disease risk Ehret et al.32 considered the causal effects of systolic blood pressure (SBP) and diastolic blood pressure (DBP; both measured in mmHg) on coronary artery disease (CAD) risk using 29 uncorrelated genetic variants.”
- 11β-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. (2013, background): “However, other studies in black subjects have been negative (764), and the gene has not emerged as a general candidate for hypertension from genome-wide association studies (182).”
- PRSice: Polygenic Risk Score software (2014, background): “…including polygenic Mendelian Randomisation (Hung et al. , 2014), where causality of potential intermediate phenotypes in a disease pathway can be tested (Ehret et al. , 2011), use of PRS as biomarkers, and the enrolment of clinical trial participants according to risk (Hu et al. , 2013).”