Understanding the Molecular and Biological Basis of GWAS Findings in AMD

Rinki Ratnapriya, PhD Baylor College of Medicine


John Timothy Stout, MD, PhD


We aim to integrate the GWAS findings with functional genomics to elucidate the mechanistic understanding of the genetic causes of AMD. The interpretation of GWAS findings remains challenging as the majority of disease-associated variants reside in the non-coding genome. In this proposal, we will integrate the GWAS findings with functional genomics to identify underlying causal variants, regulatory elements, and target genes to address major gaps in mechanistic understanding of the causes of AMD. Additionally, we will characterize the cis-regulatory landscape in non-human primates for gaining insights into the primate-specific regulatory circuitry that can ultimately serve as a template for developing animal models of AMD.

Project Details

AMD has a substantial genetic basis that has been successfully demonstrated through several GWAS. However, this information has not been exhausted for understanding the mechanistic basis of the disease or to provide new opportunities for therapeutic discovery. Our approach to systematically characterize gene expression across cell types and the regulatory elements that control them are aimed to provide an innovative strategy to explore the molecular mechanisms through which non-coding genetic variants affect AMD risk. Our project aims to obtain a mechanistic understanding of the biology underlying genetic associations that could potentially uncover novel genes and pathways for therapeutic interventions. Our findings provide a systems-level understanding of the disease, and tools and resources generated will also be relevant for functional genomic dissection of other related complex ocular diseases. Finally, these findings will eventually improve the clinical interpretation of GWAS studies in risk prediction and clinical trials practices.