Ambient PM_2.5 exposure and sleep quality: Evidence from circadian DNA methylation signatures in a population-based...

Sleep disturbance is prevalent in aging populations, yet its association with ambient PM_2.5 remains insufficiently characterized due to the lack of reliable molecular biomarkers. We leveraged 2350 middle-aged and older adults from the Guangxi Eco-Environmental Health and Aging Study to examine the association between PM_2.5 exposure and sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) and to identify relevant DNA methylation signatures of circadian rhythm genes. Higher PM_2.5 was significantly associated with worse sleep outcomes, with the strongest associations for the 2-month exposure window. Particularly, per 10 μg/m³ increase in the 2-month average PM_2.5 was associated with a 1.33-point increase in PSQI score (95% CI: 0.95, 1.71), a 0.79-hour reduction in sleep duration (95% CI: -0.99, -0.59), and higher odds of poor sleep quality (odds ratio [OR] =2.17, 95% CI: 1.69, 2.80) and abnormal sleep duration (OR =1.59, 95% CI: 1.24, 2.03). A two-stage analysis of DNA methylation signatures identified 47 sleep-related CpG sites, of which 11 were selected using LASSO penalization to construct the sleep-quality-related methylation risk score (MRS). Mediation analyses further identified five CpGs annotated to NPAS2, PRKAG2, RORA, and CSNK2A2 that partially mediated the association between PM_2.5 exposure and sleep quality (mediation proportions: 9.08%-15.98%), whereas the sleep MRS accounted for a higher mediation proportion than individual CpGs (25.03%). Our findings underscore ambient PM_2.5 exposure as a relevant environmental factor linked to impaired sleep quality and highlight that circadian epigenetic signatures could serve as molecular markers of vulnerability to pollution-related sleep disturbances.