The Causal Relationships Between Sleep-related Phenotypes and Body Composition: A Mendelian Randomized Study

Abstract

Background: Despite cumulative evidence showing obesity is associated with changes in sleep quality and quantity, the study about the relationships between sleep and body composition is scarce, and whether the relationship is causal remains unknown. In this study, we examined whether there are causal associations between sleep and body composition.

Methods: First, we estimated genetic correlations between sleep-related phenotypes and body composition using the linkage disequilibrium score regression (LDSC). Mendelian randomization (MR) analysis was then conducted to test 2-way causal relationships on phenotypes with significant genetic associations. Finally, Bayesian colocalization (COLOC) analysis was performed to calculate the posterior probability of causal variation and identify the common genes to verify the results of MR.

Results: For the LDSC analysis, we observed some significant genetic correlations (rG), such as snoring and right leg fat mass (rG = 0.376, P = 7.21 × 10-80). For the MR analysis, we identified some significant causal relationships, such as snoring is the causal risk factor for whole-body fat-free mass (Pweighted median = 1.28 × 10-6, PMR-PRESSO = 1.35 × 10-7), dozing is the causal risk factor for right leg fat mass (Pweighted median = 9.22 × 10-4, PMR-PRESSO = 9.55 × 10-4), and right arm fat mass (Pweighted median = 1.11 × 10-40, PMR-PRESSO = 4.93 × 10-55) is the causal risk factor for snoring. For the COLOC analysis, we identified rs143384 mapping on GDF5 and 6 overlapped single nucleotide polymorphisms (eg, rs1421085, rs11642015) mapping on FTO.

Conclusion: Our study identified the causal relationships between sleep-related phenotypes and body composition. These findings may give insights into the mechanism of sleep disturbances and provide novel therapeutic targets.

Keywords: FTO; GDF5; fat mass; fat-free mass; sleep.