The Pros and Cons of Mendelian Randomization Studies to Evaluate Emerging Cardiovascular Risk Factors

Abstract

Mendelian randomization (MR) is a technique that uses natural genetic variation to assess the potential causal role of a modifiable risk factor on cardiovascular disease. Advances have led to the identification of single nucleotide polymorphisms linked with risk factors that act as naturally randomized instruments to investigate the risk factor-disease relationship. There are several pros and cons when using MR. It can address many limitations of observational study design including confounding, reverse causation, and demonstration of causality when a randomized controlled trial is not practical or feasible. However, several limitations do exist and include pleiotropy (multiple downstream effects of a single genetic variant), linkage disequilibrium (non-random association of genetic variation), and imprecise estimates of causal effects. MR is an important tool in cardiovascular research and has been applied to assess cardiovascular risk factors including obesity and atrial fibrillation. While these studies provide insight into disease causation, understanding the strengths and limitations of the technique is important for appropriate interpretation of results.