Efstathiadou, A., Gill, D., McGrane, F., Quinn, T. and Dawson, J. (2019) Genetically determined uric acid and the risk of cardiovascular and neurovascular diseases: a Mendelian randomization study of outcomes investigated in randomized trials. Journal of the American Heart Association, 8, e012738. (doi: 10.1161/JAHA.119.012738) (PMID:31438759) (PMCID:PMC6755826)
|
Text
190404.pdf - Published Version Available under License Creative Commons Attribution Non-commercial No Derivatives. 2MB |
Abstract
Background: Higher serum uric acid levels are associated with cardiovascular and neurovascular disease, but whether these relationships are causal is not known. We applied Mendelian randomization approaches to assess the association between genetically determined uric acid levels and outcomes under study in large clinical trials. Methods and Results: We used 28 genetic variants related to serum uric acid as instruments to perform a range of 2‐sample Mendelian randomization methods. Our analysis had statistical power to detect clinically relevant effects of genetically determined serum uric acid levels on the considered clinical outcomes; cognitive function, Alzheimer disease, coronary heart disease, myocardial infarction, systolic blood pressure, and stroke. There was some suggestive evidence for an association between higher genetically determined serum uric acid and cognitive function. There was also some suggestive evidence of a relationship between coronary heart disease, systolic blood pressure, and the serum uric acid genetic instruments, but likely related to genetic pleiotropy. Overall, there was no consistent evidence of a clinically relevant effect of genetically determined serum uric acid on any of the considered outcomes. Conclusions: This Mendelian randomization study does not support a clinically relevant causal effect of genetically determined serum urate on a range of cardiovascular and neurovascular outcomes. The weak association of genetically determined serum urate with coronary heart disease and systolic blood pressure may be because of pleiotropic effects. If urate lowering drugs such as allopurinol are found to affect the
| Item Type: | Articles |
|---|---|
| Additional Information: | Dr Gill is funded by the Wellcome Trust 4i programme at Imperial College London. Dr Quinn is supported by a Joint Chief Scientist Office and Stroke Association Senior Clinical Lectureship. The MEGASTROKE project received funding from sources specified at http://www.megastroke.org/acknowledgments.html. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Dawson, Professor Jesse and Quinn, Professor Terry |
| Authors: | Efstathiadou, A., Gill, D., McGrane, F., Quinn, T., and Dawson, J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Journal of the American Heart Association |
| Publisher: | Wiley |
| ISSN: | 2047-9980 |
| ISSN (Online): | 2047-9980 |
| Published Online: | 23 August 2019 |
| Copyright Holders: | Copyright © 2019 The Authors |
| First Published: | First published in Journal of the American Heart Association 8:e012738 |
| Publisher Policy: | Reproduced under a Creative Commons license |
University Staff: Request a correction | Enlighten Editors: Update this record
Deposit and Record Details
Deposit and Record Details