The Promise of Mendelian Randomization in Parkinson’s Disease: Has the Smoke Cleared Yet for Smoking and Parkinson’s Disease Risk?

Abstract

This commentary discusses the strengths and limitations of utilizing the Mendelian randomization (MR) approach in Parkinson’s disease (PD) studies. Epidemiologists proposed to employ MR when genetic instruments are available that represent reliable proxies for modifiable lifelong exposures which elude easy measurement in studies of late onset diseases like PD. Here, we are using smoking as an example. The great promise of the MR approach is its resilience to confounding and reverse causation. Nevertheless, the approach has some drawbacks such as being liable to selection- and survival-bias, it makes some strong assumptions about the genetic instruments employed, and requires very large samples size. When interpreted carefully and put into the context of other studies that take both genetics and the environment into consideration, MR studies help us to not only ask interesting questions but also can support causal inference and provide novel insights.