Nov 5, 2018

Genetic variants related to antihypertensive targets inform drug efficacy and side effects

BioRxiv : the Preprint Server for Biology
Dipender GillIoanna Tzoulaki

Abstract

Background: Drug effects can be investigated through natural variation in the genes for their protein targets. We aimed to use this approach to explore the potential side effects and repurposing potential of antihypertensive drugs, which are amongst the most commonly used medications worldwide. Methods: We identified genetic instruments for antihypertensive drug classes as variants in the gene for the corresponding target that associated with systolic blood pressure at genome-wide significance. To validate the instruments, we compared Mendelian randomisation (MR) estimates for drug effects on coronary heart disease (CHD) and stroke risk to randomised controlled trial (RCT) results. Phenome-wide association study (PheWAS) in the UK Biobank was performed to identify potential side effects and repurposing opportunities, with findings investigated in the Vanderbilt University Biobank (BioVU) and in observational analysis of the UK Biobank. Findings: We identified suitable genetic instruments for beta-blockers (BBs) and calcium channel blockers (CCBs). MR estimates for their effect on CHD and stroke risk respectively were comparable to results from RCTs against placebo. PheWAS in the UK Biobank identified an association of the CCB g...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Observational Study
Mendelian Randomization Analysis
Magnetic Resonance Imaging
Genome
Genes
Systolic Blood Pressure Measurement
Diverticulosis
Coronary Arteriosclerosis
Controlled Clinical Trials, Randomized

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