Genetically Supported Causality between Brain Structural Connectome and Sleep Duration in Children: A Two-Sample Mendelian Randomization Study

Certain structural brain connections have been confirmed to influence sleep duration in children. However, the causal relationships between all brain regions and children's sleep duration remain unclear. A two-sample Mendelian randomization analysis was conducted using data from genome-wide association studies (GWAS) to examine the relationships between 206 structural connections and sleep duration in children. Sensitivity analyses were employed to validate the findings and assess the robustness of the causal inferences. Stronger connectivity from the left hemisphere (LH) control network to the accumbens (<i>β</i> = -0.15; 95% CI = [-0.30, -2.88 × 10^-3]; <i>p</i> = 0.05) and from the LH somatomotor network to the LH default network (<i>β</i> = -0.18; 95% CI = [-0.34, -0.03]; <i>p</i> = 0.02) in white-matter structural connectivity (SC) were associated with shorter sleep durations. Conversely, increased white-matter SC from the LH dorsal attention network to the thalamus (<i>β</i> = 0.14; 95% CI = [8.45 × 10^-4, 0.27]; <i>p</i> = 0.05), from the right hemisphere (RH) control network to the thalamus (<i>β</i> = 0.10; 95% CI = [0.01, 0.19]; <i>p</i> = 0.03), from the RH default network to the thalamus (<i>β</i> = 0.08; 95% CI = [4.53 × 10^-3, 0.16]; <i>p</i> = 0.04), from the RH limbic network to the thalamus (<i>β</i> = 0.15; 95% CI = [0.05, 0.26]; <i>p</i> = 3.77 × 10^-3), and from the RH somatomotor network to the thalamus (<i>β</i> = 0.20; 95% CI = [0.07, 0.32]; <i>p</i> = 1.63 × 10^-3) correlated with longer sleep durations in children. Two-sample Mendelian randomization provides novel insights into the relationships between brain regions and sleep duration in children. Our findings demonstrate a causal relationship between specific brain areas and sleep duration.