Multi-omics Integration in AMD: the CFH Gene Case Study

Abstract

Age-related macular degeneration (AMD) is a progressive retinal disease and a leading cause of irreversible blindness in older adults, imposing a substantial global health burden. Genome-wide association studies (GWAS) have identified over 50 loci associated with AMD, yet most lie in non-coding regions, obscuring the underlying molecular mechanisms. This paper highlights the application of multiomics integration—a framework that combines genetic associations with regulatory and functional outcomes across molecular layers—to elucidate the genetic risk of AMD, with a particular focus on the CFH gene, a central player in AMD pathogenesis. This study first summarizes key omics data types (genomics, transcriptomics, epigenomics) and core analytical tools, such as colocalization analysis and expression quantitative trait loci (eQTL) mapping. This then examines CFH-centered multi-omics findings, including evidence of shared causal variants between AMD GWAS and CFH eQTLs, and tissue-specific regulatory effects observed in the liver and retinal pigment epithelium. The discussion further extends to other AMD loci (e.g., ARMS2/HTRA1, C3) and outlines technical challenges such as data heterogeneity, tissue accessibility and translational potential. Overall, despite existing complexities, multi-omics integration provides an essential bridge between genetic associations and disease mechanisms, offering a roadmap for improved risk prediction and the development of mechanism-driven, biomarker-based therapeutics for AMD.