Sleep disorders causally affect the brain cortical structure: A Mendelian randomization study.

ABSTRACT

BACKGROUND: s Previous studies have reported that patients with sleep disorders have altered brain cortical structures. However, the causality has not been determined. We performed a two-sample Mendelian randomization (MR) to reveal the causal effect of sleep disorders on brain cortical structure. METHODS: We included as exposures 11 phenotypes of sleep disorders including subjective and objective sleep duration, insomnia symptom and poor sleep efficiency, daytime sleepiness (narcolepsy)/napping, morning/evening preference, and four sleep breathing related traits from nine European-descent genome-wide association studies (GWASs). Further, outcome variables were provided by ENIGMA Consortium GWAS for full brain and 34 region-specific cortical thickness (TH) and surface area (SA) of grey matter. Inverse-variance weighted (IVW) was used as the primary estimate whereas alternative MR methods were implemented as sensitivity analysis approaches to ensure results robustness. RESULTS: At the global level, both self-reported or accelerometer-measured shorter sleep duration decreases the thickness of full brain both derived from self-reported data (ßIVW = 0.03 mm, standard error (SE) = 0.02, P = 0.038; ßIVW = 0.02 mm, SE = 0.01, P = 0.010). At the functional level, there were 66 associations of suggestive evidence of causality. Notably, one robust evidence after multiple testing correction (1518 tests) suggests the without global weighted SA of superior parietal lobule was influenced significantly by sleep efficiency (ßIVW = -285.28 mm2, SE = 68.59, P = 3.2 × 10-5). CONCLUSIONS: We found significant evidence that shorter sleep duration, as estimated by self-reported interview and accelerometer measurements, was causally associated with atrophy in the entire human brain.