Imperial College London
Alternate

ProfessorPaulElliott

Faculty of Medicine, School of Public Health

Chair in Epidemiology and Public Health Medicine
 
 
 
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Contact

 

+44 (0)20 7594 3328p.elliott Website

 
 
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Assistant

 

Miss Jennifer Wells +44 (0)20 7594 3328

 
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Location

 

154Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gill:2019:10.1161/CIRCULATIONAHA.118.038814,
author = {Gill, D and Georgakis, MK and Koskeridis, F and Jiang, L and Wei, WQ and Theodoratou, E and Elliott, P and Denny, JC and Malik, R and Evangelou, E and Dehghan, A and Dichgans, M and Tzoulaki, I},
doi = {10.1161/CIRCULATIONAHA.118.038814},
journal = {Circulation},
pages = {270--279},
title = {Use of genetic variants related to antihypertensive drugs to inform on efficacy and side effects},
url = {http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038814},
volume = {140},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Drug effects can be investigated through natural variation in the genes for their protein targets. The current study 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: Genetic proxies for the effect of antihypertensive drug classes were identified as variants in the genes for the corresponding targets that associated with systolic blood pressure (SBP) at genome-wide significance. Mendelian randomization (MR) estimates for drug effects on coronary heart disease (CHD) and stroke risk were compared to randomized 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.Results: Suitable genetic proxies for angiotensin-converting-enzyme inhibitors (ACEIs), beta-blockers (BBs) and calcium channel blockers (CCBs) were identified. 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 standardized genetic risk score with increased risk of diverticulosis (odds ratio [OR] 1.02 per standard deviation increase, 95%CI 1.01-1.04), with a consistent estimate found in BioVU (OR 1.01, 95%CI 1.00-1.02). Cox regression analysis of drug use in the UK Biobank suggested that this association was specific to non-dihydropyridine CCBs (hazard ratio [HR] 1.49 considering thiazide diuretics as a comparator, 95%CI 1.04-2.14), but not dihydropyridine CCBs (HR 1.04, 95%CI 0.83-1.32). Conclusions: Genetic variants can be used to explore the efficacy and side effects of antihypertensive medications. The identified potential effect of non-dihydropyridine CCBs on diverticulosis risk could have cli
AU  - Gill,D
AU  - Georgakis,MK
AU  - Koskeridis,F
AU  - Jiang,L
AU  - Wei,WQ
AU  - Theodoratou,E
AU  - Elliott,P
AU  - Denny,JC
AU  - Malik,R
AU  - Evangelou,E
AU  - Dehghan,A
AU  - Dichgans,M
AU  - Tzoulaki,I
DO  - 10.1161/CIRCULATIONAHA.118.038814
EP  - 279
PY  - 2019///
SN  - 0009-7322
SP  - 270
TI  - Use of genetic variants related to antihypertensive drugs to inform on efficacy and side effects
T2  - Circulation
UR  - http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038814
UR  - http://hdl.handle.net/10044/1/70444
VL  - 140
ER  -
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