Mendelian randomisation for psychiatry: how does it work, and what can it tell us?

Abstract

The successful prevention of mental illness relies upon the identification of causal, modifiable risk factors. However, observational evidence exploring such risk factors often produces contradictory results and randomised control trials are often expensive, time-consuming or unethical to conduct. Mendelian randomisation (MR) is a complementary approach that uses naturally occurring genetic variation to identify possible causal effects between a risk factor and an outcome in a time-efficient and low-cost manner. MR utilises genetic variants as instrumental variables for the risk factor of interest. MR studies are becoming more frequent in the field of psychiatry, warranting a reflection upon both the possibilities and the pitfalls. In this Perspective, we consider several limitations of the MR method that are of particular relevance to psychiatry. We also present new MR methods that have exciting applications to questions of mental illness. While we believe that MR can make an important contribution to the field of psychiatry, we also wish to emphasise the importance of clear causal questions, thorough sensitivity analyses, and triangulation with other forms of evidence.