Investigating the link between genetic predictive factors of brain functional networks and two specific sleep disorders: Sleep apnoea and snoring.

Background: Sleep disorders are a widespread public health issue globally. Investigating the causal relationship between resting-state brain functional abnormalities and sleep disorders can provide scientific evidence for precision medicine interventions.

Methods: We screened single nucleotide polymorphisms (SNPs) associated with rs-fMRI phenotype as instrumental variables Using bidirectional two-sample Mendelian randomization (MR), mediation MR, and multivariate MR based on Bayesian methods, the study tested the causal relationship between genetically predicted rs-fMRI and nine common sleep disorders.

Results: The main inverse variance weighted (IVW) analysis identified four resting state functional magnetic resonance imaging (rs-fMRI) phenotypes that are causally associated with the risk of sleep disorders. For example, increased amplitude in nodes of the parietal, precuneus, occipital, temporal, and cerebellum regions, as well as the default mode network (DMN), central executive network (CEN) and attention network (AN) was associated with an increased risk of sleep apnoea. Enhanced neural activity in the calcarine or lingual and cerebellum regions and increased functional connectivity with the visual and subcortical-cerebellum networks was associated with a reduced risk of snoring. The mediation MR analysis shows that, body mass index (BMI) plays a significant mediating role in the risk of sleep apnoea by modulating the amplitude of nodes in the parietal, temporal, and cerebellum regions, as well as the connectivity changes in the DMN, CEN, and AN.

Conclusions: This study identified three rs-fMRI phenotypes linked to increased sleep apnoea risk and one associated with decreased snoring risk, providing an important target for the treatment of sleep disorders at the level of brain functional networks.