Research Techniques Made Simple: Using Genetic Variants for Randomization

Observational epidemiological studies have identified associations between a number of modifiable exposures and outcomes, including in dermatology, such as between smoking and psoriasis. However, it is challenging to determine if such relationships are causal, due to the potential of confounding and reverse causation. Mendelian Randomization (MR) is a statistical method which can be used to investigate the causal relationships between an exposure and outcome, by using a genetic instrument that proxies the exposure. The resulting estimate (under certain assumptions) can be interpreted as the causal estimate, free of confounding and reverse causation. In this review, we provide an overview of how to undertake an MR analysis, with examples from the dermatology literature. We also discuss the challenges and future directions of this method.