Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Randomized controlled trials and Mendelian randomization studies are two study designs that provide randomized evidence in human biological and medical research. Both exploit the power of randomization to provide unconfounded estimates of causal effect. However, randomized trials and Mendelian randomization studies have very different study designs and scientific objectives. As a result, despite sometimes being referred to as "nature's randomized trial," a Mendelian randomization study cannot be used to replace a randomized trial but instead provides complementary information. In this review, we explain the similarities and differences between randomized trials and Mendelian randomization studies, and suggest several ways that Mendelian randomization can be used to directly inform and improve the design of randomized trials illustrated with practical examples. We conclude by describing how Mendelian randomization studies can employ the principles of trial design to be framed as "naturally randomized trials" that can provide a template for the design of future randomized trials evaluating therapies directed against genetically validated targets.

Original publication




Journal article


Cold Spring Harb Perspect Med

Publication Date