Jan 14, 2020

Identification of Circulating Proteins Associated with Blood Pressure Using Mendelian Randomization

Circulation. Genomic and Precision Medicine
Sébastien ThériaultGuillaume Paré

Abstract

Background - Hypertension is a common modifiable risk factor for cardiovascular disease and mortality. Pathophysiological mechanisms leading to hypertension remain incompletely understood. Mendelian randomization (MR) allows the evaluation of the causal role of markers by minimizing the risk of biases such as reverse causation and confounding. We aimed to identify novel circulating proteins associated with blood pressure through a comprehensive screen of 227 blood biomarkers using MR. Methods - Genetic determinants of 227 biomarkers were identified in Outcome Reduction with Initial Glargine Intervention (ORIGIN; NCT00069784) participants (N=4,147) and combined with genetic effects on systolic, diastolic, mean arterial and pulse pressure (SBP, DBP, MAP and PP) from the International Consortium for Blood Pressure (ICBP; 74,064 individuals) using MR. Results were replicated in the UK Biobank (up to 319,103 individuals) and using another biomarker dataset (N=3,301). MR analyses with cardiovascular risk factors and outcomes as well as other biomarkers were performed to further evaluate the mechanisms involved. Results - Six biomarkers were associated with blood pressure using MR after adjustment for multiple hypothesis testing. Rela...Continue Reading

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Mentioned in this Paper

Systolic Pressure
Diastole
Evaluation
Biomaterials
Fibronectins
Arteries
Proline
Brain
Body Mass Index
Entity - Organization

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