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

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.
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.
Univariable MR showed that higher genetically predicted basal metabolic rate, body mass index, and whole-body fat mass were each associated with increased OSA risk (IVW odds ratio per SD: basal metabolic rate 1.85, 95% CI 1.62–2.10; body mass index 2.27, 95% CI 2.07–2.49; whole-body fat mass 2.05, 95% CI 1.85–2.28; all p < 0.05). In multivariable MR, the association between basal metabolic rate and OSA was fully attenuated after adjusting for adiposity (p > 0.05), whereas body mass index and whole-body fat mass retained strong independent causal effects (both p < 0.05), indicating that the apparent basal metabolic rate–OSA association is entirely mediated by fat mass. Reverse MR suggested that genetic liability to OSA modestly increases basal metabolic rate (OR = 1.08, 95% CI 1.04–1.12, p < 0.05), although this estimate showed partial sensitivity to pleiotropy.
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.
This study utilizes Mendelian randomization to clarify the causal relationship between basal metabolic rate (BMR) and obstructive sleep apnea (OSA), addressing a gap in understanding metabolic risks.
We demonstrate that BMR does not independently increase OSA risk; rather, the association is entirely mediated by body fat accumulation.
The findings reveal a bidirectional link where genetic liability to OSA modestly increases BMR, offering new insights into the complex metabolic mechanisms underlying sleep disorders.
Obstructive sleep apnea (OSA) is a sleep disorder in which breathing repeatedly stops during the night. It can lead to poor sleep, daytime tiredness, and long-term health problems. OSA is strongly linked to obesity, but it is less clear whether a person’s natural “metabolic rate” plays a direct role. In this study, we analyzed genetic data from very large population studies to better understand what truly causes OSA. Genetic information can help researchers study cause and effect more reliably, because genes are set at birth and are not influenced by lifestyle later in life. Our results show that higher body fat clearly increases the risk of developing OSA. Although people with higher resting energy use seemed more likely to have OSA at first, this link disappeared once body fat was taken into account. This suggests that body fat—not metabolic rate itself—is the key factor. We also found some early evidence that OSA might slightly affect how much energy the body uses, but this needs more research. Overall, maintaining a healthy body weight remains one of the most important ways to reduce the risk of sleep apnea and improve overall health.