Navigating Mendelian Randomization in Sleep Medicine: Challenges, Opportunities, and Best Practices.

Mendelian randomization (MR) has become an influential method for elucidating causal links between sleep traits and disorders, and health outcomes. This article provides sleep medicine specialists with an overview of MR, emphasizing its applications and limitations in health research, particularly in the context of sleep research. The article addresses key challenges in conducting and interpreting MR studies on sleep, focusing on the core assumptions of relevance, exchangeability, and exclusion restriction. The importance of proper genetic instrument selection, bias mitigation, and cautious result interpretation is emphasized. Strategies are recommended to enhance the quality of MR studies in sleep medicine, including collaborations between MR experts and sleep specialists. The paper also explores sleep medicine-specific issues like analyzing binary traits and addressing heterogeneity in pooled analyses. Guidance is provided on transparent reporting of MR findings, stressing the need for comprehensive effect estimates, confidence intervals, and p-values. We conclude by advocating for rigorous MR implementation in sleep research to deepen our understanding of sleep-health relationships. By following best practices in study design, analysis, and reporting, researchers can reinforce the credibility and impact of MR findings in sleep medicine, ultimately improving patient care and public health strategies.