Risk factors of primary angle-closure glaucoma: An exposome-wide association study in the China Kadoorie Biobank.

PURPOSE: Primary angle-closure glaucoma (PACG) is a leading cause of irreversible blindness in Asia. Although traditionally considered an anatomical ocular disorder, the contribution of systemic metabolic, vascular, and lifestyle factors to PACG development remains unclear. METHODS: Using data from the China Kadoorie Biobank (CKB), involving 499,102 participants aged 30-79 years at baseline, we explored associations of 117 exposures, including socio-demographics, lifestyle patterns, medical history, and physical measurements, with probable PACG (prob PACG) incidence. Elastic-Net, XGboost, and Cox regression methods were employed. RESULTS: Over a median follow-up of 15.7 years, 3,266 incident prob PACG cases were ascertained. After correcting for multiple testing, 26 factors were independently associated with prob PACG. Age, female sex, and postmenopausal status showed the strongest positive associations with pro PACG. Notably, several markers of metabolic and vascular ageing-including diabetes, higher random plasma glucose, larger waist circumference, and elevated pulse pressure-were independently associated with higher risk, whereas BMI was inversely associated (all P<0.01). In addition, daily intake of dairy products and daily preserved vegetables, and peptic ulcer were associated with a higher risk, while higher physical activity and weekly tea consumption were associated with lower risk. No significant associations were found for hypertension, SBP, or DBP with prob PACG. CONCLUSIONS: Our findings suggest that PACG may be influenced not only by anatomical susceptibility but also by broader metabolic, vascular, and lifestyle factors. The clustering of several strong associations around markers of metabolic and vascular ageing provides new insights into PACG aetiology and may help identify priorities for future studies of risk stratification and prevention.