The Role of Gene Expression Regulation on Genetic Risk of Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in the elderly. It is a complex multifactorial disease that is caused by the cumulative impact of genetic predisposition, environmental stress, and advanced aging. Knowledge of genetic risk factors underlying AMD susceptibility has advanced rapidly in the past decade that can be largely credited to genome-wide association studies (GWAS) and next-generation sequencing (NGS) efforts. GWAS have identified 34 genetic risk loci for AMD; the majority of which are in the noncoding genome. Several lines of evidence suggest that a complex trait-associated variant is likely to regulate the gene expression (acting as expression quantitative trait loci (eQTLs)), and there is a significant enrichment of GWAS-associated variants within eQTLs. In the last two years, eQTL studies in AMD-relevant tissues have provided functional interpretation of several AMD-GWAS loci. This review highlights the knowledge gained to date and discusses future directions to bridge the gap between genetic predisposition and biological mechanisms to reap the full benefits of GWAS findings.

Keywords: Age-related macular degeneration; Biomarkers; GWAS; Gene expression regulation; Gene regulatory networks; Transcriptome; eQTL.