Abstract
ABSTRACT Background To evaluate the associations of systemic diseases with AMD incidence and explore whether polygenic risk score (PRS) for AMD influences these associations. To assess the impacts of polymorbidities and serum biomarkers on AMD risk. Methods This prospective study of 471156 AMD-free UK Biobank participants assessed systemic diseases (hypertension, diabetes, cardiovascular disease [CVD], dyslipidemia, chronic kidney disease [CKD], and dementia) and AMD incidence using multivariable Cox proportional hazard models. Results Five systemic diseases were associated with an increased risk of AMD incidence, including hypertension (fully adjusted HR = 1.13, 95% CI: 1.09-1.18; false discovery rate [FDR]-corrected p = 3.41 × 10 −8 ), diabetes (HR = 1.48, 95% CI: 1.38-1.58; p = 3.79 × 10 −27 ), CVD (HR = 1.13, 95% CI: 1.08-1.18; p = 7.60 × 10 −8 ), dyslipidemia (HR = 1.11, 95% CI: 1.05-1.16; p = 1.28 × 10 −4 ), and CKD (HR = 1.22, 95% CI: 1.07-1.39; p = 0.006), whereas dementia showed no association ( p = 0.74). AMD PRS modified the association with diabetes, but not with the other diseases. The risk of AMD incidence increased in participants with one to five comorbidities ( p for trends < 0.001), compared to those without. Serum biomarkers related to lipid regulation, inflammation, glycemic control, renal function, and nutrition were associated with AMD incidence. Conclusions Major systemic diseases elevate AMD risk, compounded by comorbidities. Serum biomarkers further implicate systemic health in AMD. Holistic health management and regular ocular screenings are crucial for AMD patients and those with systemic diseases.