Multivariate genetic architecture of age-related eye disease

Abstract

At present, the genetic architecture underlying traits linked to Age-related eye disease (ARED) remains largely unexplored. We utilized Genomic Structural Equation Modeling (Genomic-SEM) and various Post-processing analysis of Genome-Wide Association Studies (GWAS) to identify statistically prioritized candidate single nucleotide polymorphisms (SNPs) associated with independent ARED variants. A total of 11 genome-wide significant loci were identified in the study. By applying diverse transcriptome-wide association approaches, we analyzed tissue-, cell layer-, and genomic element-associated gene signals reflecting age-related ocular vulnerabilities, alongside their functional annotations in relation to ARED. Through conducting a GWAS on a phenotype not directly measured, our research presents the first comprehensive genetic landscape of ARED.