Long-Term PM₂.₅ Constituents Exposure, Genetic Susceptibility, and Incident Sleep Apnea: A Prospective Cohort Study.

Abstract

Sleep apnea (SA), a widespread disorder linked to heart disease, affects over 1 billion people globally. While PM₂.₅ is suspected to worsen this condition, the specific role of individual PM₂.₅ constituents-how genetics might amplify their harm-remains unclear. Do long-term exposures to PM₂.₅ constituents (EC, OM, SO₄^2-, NO₃^-, NH₄⁺) associate with incident SA, and does genetic susceptibility modify these associations? In this prospective cohort study of 495,073 UK Biobank participants, PM₂.₅ constituents were modeled via the European Monitoring and Evaluation Programme model for the UK, driven by Weather and Research Forecast model meteorology. Time-dependent Cox regression and quantile-based g-computation models (QGC) were employed for analysis. A genome-wide significant SNP (rs9937053) for SA identified in the UK Biobank database was selected to analyze its interaction with PM₂.₅ constituents. In the analysis of 495,073 participants with a median of 11.82-year follow-up, 7,086 incident SA cases were identified. The adjusted hazard ratios (HRs) of SA for each interquartile range increase in PM₂.₅, EC, OM, NH₄⁺, NO₃^-, and SO₄^2- were 1.16 (1.15 to 1.18), 1.11 (1.09 to 1.12), 1.08 (1.07 to 1.09), 1.21 (1.19 to 1.23), 1.18 (1.17 to 1.19), and 1.11 (1.09 to 1.12). QGC modeling identified SO₄^2- as the predominant contributor to PM₂.₅-associated SA risk (58% proportion explained). Stratified analyses identified heightened susceptibility among urban residents (p_interaction <0.05 for PM₂.₅, NO₃^-) and obese individuals (BMI ≥30; p_interaction <0.05 for PM₂.₅, EC, OM, NH₄⁺, SO₄^2-). Moreover, the rs9937053 SNP significantly interacts with PM₂.₅ constituents on SA risk. PM₂.₅ constituents-particularly SO₄^2--elevate SA risk, with urban populations, obese individuals, and rs9937053 carriers at greatest vulnerability. These findings demonstrate SA risk from PM₂.₅ at concentrations exceeding the WHO guideline. They advocate for an urgent emission control of sulfate (gas and oil combustion) as a priority. N/A (Observational study).