Differential associations of lipid profile and genetic susceptibility with sleep duration

BACKGROUND: Lipid metabolism is influenced by multiple factors, and its association with sleep duration may vary across lipid fractions. Lipid levels and their genetic susceptibility have been associated with sleep duration; however, these associations are heterogeneous, and it remains unclear whether specific lipid components exhibit more consistent associations with sleep duration. METHODS: This study included 410,493 participants from the UK Biobank. Multivariable linear regression (MLR) was used to assess the associations of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) with sleep duration. Polygenic risk scores (PRSs) were incorporated to evaluate genetic susceptibility. Interaction terms between lipid levels and PRSs were included in multivariable models. Cox proportional hazards models were used to examine the associations of lipid levels and PRSs with sleep disorders. Joint exposure analyses of lipid levels and PRSs were performed, and interaction effects were assessed. Restricted cubic spline models were further applied to evaluate potential non-linear associations. Proteomic analyses were conducted to explore proteomic features associated with both lipid profile and sleep duration. RESULTS: MLR analyses showed that TG levels were positively associated with sleep duration (β = 0.027, P < 0.001), whereas TC levels were inversely associated with sleep duration (β = -0.005, P = 0.005). No significant association was observed for LDL. In contrast, PRSs for TG, TC, and LDL were consistently inversely associated with sleep duration. A significant interaction was observed between TG and their PRS (β = -0.009, p < 0.001). TG and PRS-TG were associated with higher risks of sleep disorders (6.9% and 3.2% per unit increase), with a significant interaction (p = 0.014). Elevated risks were observed in high TG groups, while TC and LDL were not significant. Both lipid traits and sleep duration were mainly enriched in immune and inflammatory pathways. CONCLUSIONS: Triglycerides showed the most consistent associations with sleep duration, and TG-related genetic susceptibility may influence TG levels and their associations with sleep duration and sleep disorders.