Mendelian Randomisation for mediation analysis with multiple mediators: theory and applications

Rationale

Many of an individual’s traits are observationally associated with their health outcomes. Understanding the relationships between these factors is critical to effective public health intervention. When multiple traits are potentially associated with a disease or health outcome, it is often not clear how much of the observed effect of each single trait is due to the effect of that trait or behaviour on other traits and behaviours, which then affect the outcome, and how much is “direct” in the sense that it is not mediated by the other traits being considered.

Causal mediation analysis is one approach that can be used to determine the proportion of the effect of a trait on an outcome that is via a mediating variable. However, this method relies on many strong assumptions. An alternative approach, relying on different assumptions, is Mendelian Randomisation (MR). MR is a method of instrumental variable analysis which utilises genetic variation between individuals to help understand causal effects.

Aims & Objectives

The aim of this project is to conduct research on the strengths and limitations of MR when trying to understand the causal effects of multiple exposures on a health outcome. This will include investigation of how novel methods of MR analysis such as Multivariable MR relate to mediation analysis and developing and extend existing MR methods to deal with multiple mediators. This project will also explore possibilities of combining the two approaches.

Methods

In this PhD you will have the opportunity to work with leading researchers in the fields of population health, statistics, and Mendelian randomisation to further develop statistical methods for causal analysis based around MR mediation analysis.

This project will involve mathematical derivation of the properties of the extended methods and verification using simulation studies. This project will also involve analysis of both individual-level and summary-level data to apply the methods developed.

Although this project will be methodological in focus, the student will have the opportunity to develop a relevant application of these methods based on their personal research interests. Prospective applicants should have a strong quantitative background and an interest in developing methods for causal analysis within a population health setting; however, no particular background knowledge is required.

How to apply for this project

This project will be based in Bristol Medical School - Population Health Sciences in the Faculty of Health Sciences at the University of Bristol.

If you have secured your own sponsorship or can self-fund this PhD please visit our information page here for further information on the department of Population Health Science and how to apply.