Causal effects of basal metabolic rate and adiposity on obstructive sleep apnea: univariable, multivariable, and bidirectional Mendelian randomization evidence

BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder strongly associated with obesity, yet the causal contribution of basal metabolic rate to OSA and the directionality of the OSA-metabolism relationship remain unclear. The objective of this study was to evaluate the independent and potential bidirectional causal relationships between basal metabolic rate and adiposity-related traits with obstructive sleep apnea using Mendelian randomization. METHODS: Two-sample Mendelian randomization (MR) was performed using genome-wide association study data from predominantly European populations to evaluate the causal effects of basal metabolic rate, body mass index, and whole-body fat mass on OSA risk and to assess the reverse effects of genetic liability to OSA on basal metabolic rate. Genetic instruments were derived from the UK Biobank genome-wide association study, and the OSA outcome was obtained from a large meta-analysis genome-wide association study. Univariable MR, multivariable MR, reverse MR, and extensive sensitivity analyses (MR-Egger, weighted median, MR-PRESSO, and leave-one-out analyses) were performed. RESULTS: < 0.05), although this estimate showed partial sensitivity to pleiotropy. CONCLUSION: Elevated adiposity is the primary causal driver of OSA. Although basal metabolic rate does not independently influence OSA risk, OSA may increase resting energy expenditure, suggesting a bidirectional relationship. These findings highlight adiposity reduction as a central target for preventing and treating OSA.