Bidirectional associations between brain functional networks and sleep disorders: A bidirectional Mendelian...

The prevalence of sleep disorders has been rising over recent decades. Sleep disorders are frequently associated with disruptions in resting-state functional brain networks. Despite these associations, the direction and genetic basis of the relationships between brain functional networks and sleep disorders remain unclear. Utilizing bidirectional two-sample Mendelian randomization (MR), we examined bidirectional associations between 191 resting-state functional magnetic resonance imaging (rsfMRI) phenotypes (n = 34,691 individuals) and 8 sleep disorder phenotypes (N = 307,843-410,385 individuals). Forward MR identified 14 rsfMRI traits that showed significant associations with sleep disorder phenotypes. Notably, the inverse variance-weighted method showed that increased amplitude in the precuneus or occipital regions within the default mode or central executive network was associated with 13.2% higher odds of sleep disorders (combined; odds ratio = 1.132, 95% confidence interval: 1.064-1.204, P = 8.30 × 10-5). In addition, reverse MR identified 6 sleep disorder phenotypes with significant associations involving 18 rsfMRI traits. For example, higher genetic liability to sleep disorders (combined) was associated with a 14.2% lower strength of functional connectivity between precentral, frontal, or supplementary motor and frontal networks (odds ratio = 0.858, 95% confidence interval: 0.795-0.927, P = 9.62 × 10-5). This study identified 32 bidirectional MR associations between sleep disorders and brain functional networks, providing candidate neural circuits for future mechanistic and interventional studies of sleep disorders.