Genome-wide association study reveals genetic mechanisms underlie eye disorders and comorbidities

Abstract

Eye diseases, including cataracts, glaucoma, diabetes retinopathy, and age-related macular degeneration, are major global health challenges and leading causes of blindness. This study leveraged genome-wide association studies (GWASs) involving over 100,000 individuals, integrating data from the Taiwan Biobank and National Health Insurance Research Database, to identify genetic loci associated with disease onset. Our findings suggest that these conditions are influenced by multifactorial etiologies, as pleiotropic loci including rs10811660, rs4710941, rs2283228, and rs7646518 were identified, linking ocular diseases to metabolic conditions. Notably, a strong genetic correlation was observed between cataract and depression. Mendelian randomization analysis further demonstrated a causal effect of depression on cataract risk, implicating shared biological pathways, particularly oxytocin signaling, in disease pathophysiology. This finding revealed a functional genetic variant near the OXTR gene, highlighting its potential as a causal candidate for genetic diagnosis in precision health. By bridging the gap between genetic discovery and clinical application, this research offers critical insights into shared genetic mechanisms across diverse health domains, paving the way for innovative diagnostic and therapeutic strategies.