Chapter 10:

In this chapter, we provide a practical overview of how to perform a Mendelian randomization investigation, from the motivation and conceptualization of the research question, through to the interpretation of results. The aim of the chapter is to provide practical guidelines for performing Mendelian randomization investigations. Particularly with the advent of summarized data and the two-sample setting, performing a Mendelian randomization analysis has become relatively straightforward. The difficulty is not in performing a Mendelian randomization analysis, but rather in performing a credible analysis.

These guidelines are deliberately written as suggestions and recommendations rather than as prescriptive rules, as we believe that there is no recipe or single “right way” to perform a Mendelian randomization investigation. Best practice will depend on the aim of the investigation and the specific exposure and outcome variables.