Use of Mendelian randomization to assess the causal status of modifiable exposures for rheumatic diseases.

Abstract

The explosion in Mendelian randomization (MR) publications is hard to ignore and shows no signs of slowing. Clinician readers, who may not be familiar with jargon-ridden methods, are expected to discern the good from the many low-quality studies that make overconfident claims of causality or stretch the plausibility of what MR can investigate. We aim to equip readers with foundational concepts, contextualized using examples in rheumatology, to appraise the many MR papers that are or will appear in their journals. We highlight the importance of assessing whether exposures are under plausibly specific genetic influence, whether the hypothesized causal pathways make biological sense, and whether results stand up to replication and use of control outcomes. Quality of research can vary substantially using MR as with any design, and all methods have inherent limitations. MR studies have provided and can still contribute valuable insights in the context of evidence triangulation.