Causal Relationship Between Brain Functional Networks and Sleep Disorders: A Mendelian Randomization Study

Area of Science:

• Neuroimaging
• Sleep Medicine
• Genetics

Background:

• Brain resting-state functional network dysfunction is linked to sleep disorders, but causal evidence is lacking.
• Understanding these causal relationships is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate causal relationships between 191 resting-state functional magnetic resonance imaging (rsfMRI) phenotypes and eight sleep disorders.
• To utilize bidirectional two-sample Mendelian randomization (MR) and multivariable MR (MVMR) to assess these links, adjusting for addictive behaviors.

Main Methods:

• Analysis of genome-wide association study (GWAS) data from UK Biobank and FinnGen.
• Selection of instrumental variables (IVs) adhering to MR assumptions.
• Primary causal estimates via inverse-variance weighted (IVW) method with comprehensive sensitivity analyses.

Main Results:

• Increased functional connectivity in salience and default mode networks (insular, cingulate, frontal regions) causally linked to a 6% reduced risk of daytime napping.
• Elevated functional connectivity in default mode and central executive networks (precuneus/occipital and parietal/temporal regions) causally associated with a 16-18% increased risk of obstructive sleep apnea (OSA).
• Multivariable MR (MVMR) indicated that while coffee intake was not a confounder, smoking, alcohol, tea, and cannabis use may influence the associations.

Conclusions:

• Provides robust evidence for causal associations between specific rsfMRI phenotypes and sleep disorders.
• Suggests that brain functional networks are potential targets for non-invasive interventions for sleep disorders, especially considering addictive behaviors.