Principal Investigator: Dr Shiu Lun Ryan Au Yeung
University of Hong Kong, Hong KongTags: 51001, cardiovascular disease, diabetes, medication, Mendelian randomisation
Aim of the study
The aim of this study is to use genetics to evaluate the health impact of medication commonly used in cardiovascular disease and diabetes
Randomized controlled trials (RCTs) are the gold standard in evaluating the health effects of medication. However, conducting RCTs may expose participants to unexpected risk, especially when there have been concerns over the validity of the evidence on the putative effect of medications (e.g. biases). As such, this may pose substantial ethical issues for whether such trials should be conducted, apart from the resources required to conduct such trials.
To facilitate the discovery/repurposing of medications for treatment of other diseases, alternative methods are being development such as the use of genomics. The use of genetics has been shown to produce results comparable to randomized controlled trials regarding the health effects of medication. Wider use of this approach may help verify the health effects of medications before they are being tested in an RCT setting.
The UK Biobank is one of the most appropriate epidemiologic sources to address this issue given it is one of the largest cohort studies globally, having access to comprehensive health data, and in-depth genetic data. Such combination would allow ascertainment of various medications’ impact on health in a cost effective manner and help identify potential existing medications to be repurposed for treatment of other diseases (e.g genetic validation).
Public health impact
We anticipate findings from this study will help evaluate the health impact of medications apart from relying on a randomized controlled trial. This genetic validation study will shed light in the identification of potential medications to be repurposed for treatment of diseases, and help screen potential medications for testing in subsequent RCTs.
Project extension – March 2020
The purpose of this proposal is to use Mendelian randomization design in the UK Biobank to emulate randomized controlled trials of cardiovascular and diabetes medications, which may help clarify some of the controversies related to these medications, such as metformin’s impact on cancer risk, and the safety of other medications such as sulphonylureas and CETP inhibitors. We will also explore possible pathways which may explain the pleiotropic effects of medications such as lipid independent pathways for statin and glycemia independent pathways for metformin.
Last updated Mar 19, 2020