Modifiers and their impact on inherited retinal diseases: a review

Abstract

Background: The phenotypic variability of inherited conditions can be due to several factors including environmental, epigenetic, and genetic. One of those genetic factors is the presence of modifying loci which alter the phenotypic expression of a primary disease or phenotype-causing variant. Modifiers are known to affect penetrance, dominance, expressivity, and pleiotropy of disease. Methods: We review the literature to highlight the impact of modifiers on inherited retinal diseases. Results: Modifiers have been identified or associated with phenotypic variation in many inherited retinal diseases including retinitis pigmentosa and Stargardt disease. Despite being notoriously difficult to identify, proposed candidate modifiers have been identified using multiple methods including GWAS, family and population studies, and variant calling methods. Conclusions: Overall, modifiers present themselves as an interesting target for further understanding of underlying disease pathways that could ultimately lead to therapeutic targets.