Understanding Mendelian Randomization.

Bentz, Garrison P; Lambrechts, Mark J · Clin Spine Surg · 2025

review · Level V

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Abstract

Mendelian randomization (MR) is a statistical method that is rising in popularity. Although randomized controlled trials (RCTs) remain the gold standard in terms of inferring causality, they are not always feasible due to time, ethical, and resource constraints. Therefore, MR can be used to establish causality through observational and noninterventional data coupled with large and quickly growing genome-wide association studies (GWAS), thereby overcoming the confounding limitations of observational studies. This article aims to provide the reader with a better understanding of Mendelian randomization and expand on how this method investigates causal relationships and provides examples relevant to orthopedic surgery.