Abstract:
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Age-related macular degeneration (AMD) is the major cause of blindness for the elderly populations in the developed countries. It is a polygenic and progressive neurodegenerative disease. Despite remarkable successes in discovering genetic variants associated with AMD risk, the genetic causes on its progression have not been elucidated. Using GWAS data from a large randomized trial, Age-Related Eye Disease Study (AREDS), where the participants were assessed every 6-12 months for up to 12 years, our research aims to evaluate the effects of genetic variants on the disease progression. In doing so, we derive the time intervals for progression-to-late-AMD in both eyes based on their assessment times and develop a computationally efficient copula-based score test, which explicitly models the between-eye correlation with interval censored time-to-event data. After identifying top genetic variants associated with AMD progression, we establish copula-based prediction models to predict the joint progression-free probability of two eyes within a subject.
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