Replication of the Association between Retinal Aging Clock Susceptibility Genes and Retinal Age Gap in an Asian Population: The Nagahama Study.

Purpose: To replicate previously reported genetic associations for the retinal aging clock-quantified as the retinal age gap-in an East Asian population and to assess cross-ancestry consistency of effect directions and sizes. Design: Genetic association study with candidate-single nucleotide polymorphism (SNP) replication embedded in a population-based cohort. Participants: Individuals who participated in both first and second visits of the Nagahama Study with gradable fundus photographs and genome-wide genotype data. Methods: A deep learning model fine-tuned on an independent subset (i.e., data from participants who attended only one of the 2 visits of the Nagahama Study) was used to estimate retinal age from color fundus photographs. We tested 13 previously reported lead variants; 7 were evaluable in our dataset (directly or as available leads). Linear regression models adjusted for standard covariates estimated SNP effects on the retinal age gap at the first visit. Statistical significance was set as Bonferroni-corrected Main Outcome Measures: Association of previously reported retinal aging clock SNPs with the retinal age gap; number of loci meeting replication criteria; directional concordance; cross-study effect-size correlation. Results: Age-prediction accuracy in the genetic cohort showed mean absolute error = 3.00 (first visit) and 3.42 years (second visit). Of 13 variants to be replicated, 7 were testable. The lead variant rs17713879 ( Conclusions: In an East Asian population, we replicate the Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.