Long-Term Fine Particulate Matter Constituents Exposure, Genetic Susceptibility, and Incident Sleep Apnea: A Prospective Cohort Study.

BACKGROUND

Sleep apnea (SA), a widespread disorder linked to heart disease, affects > 1 billion people globally. Although fine particulate matter (PM2.5) is suspected to worsen this condition, the specific role of individual PM2.5 constituents-how genetics might amplify their harm-remains unclear.

RESEARCH QUESTION: Are long-term exposures to PM2.5 constituents (elemental carbon [EC], organic matter [OM], sulfate, nitrate, and ammonium) associated with incident SA, and does genetic susceptibility modify these associations?

STUDY DESIGN AND

METHODS

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 (QGC) models were used for analysis. A genome-wide significant single nucleotide polymorphism (SNP), rs9937053, for SA identified in the UK Biobank database was selected to analyze its interaction with PM2.5 constituents.

RESULTS

In the analysis of 495,073 participants with a median follow-up of 11.82 years, 7,086 incident cases of SA were identified. The adjusted hazard ratios (HRs) of SA for each increase in PM2.5, EC, OM, ammonium, nitrate, and sulfate were 1.16 (interquartile range [IQR], 1.15-1.18), 1.11 (IQR, 1.09-1.12), 1.08 (IQR, 1.07-1.09), 1.21 (IQR, 1.19-1.23), 1.18 (IQR, 1.17-1.19), and 1.11 (IQR, 1.09-1.12). QGC modeling identified sulfate as the predominant contributor to PM2.5-associated SA risk (58% proportion explained). Stratified analyses identified heightened susceptibility among urban residents (P < .05 for interaction for PM2.5 and nitrate) and individuals with obesity (BMI ≥ 30 kg/m2; P < .05 for interaction for PM2.5, EC, OM, ammonium, and sulfate). Moreover, the rs9937053 single nucleotide polymorphism significantly interacts with PM2.5 constituents on SA risk.

INTERPRETATION: Our results show that PM2.5 constituents-particularly sulfate-elevate SA risk, with urban populations, individuals with obesity, and rs9937053 carriers at greatest vulnerability. These findings demonstrate SA risk resulting from PM2.5 exposure at concentrations exceeding the World Health Organization guidelines. They advocate for an urgent emission control of sulfate (gas and oil combustion) as a priority.