Disease risk assessments based on genetic variants are rapidly gaining interest in the clinical community as they have the potential to improve health outcomes for a variety of complex diseases. Polygenic risk score (PRS) or genetic risk score (GRS) is a statistical tool that measures an individual's genetic predisposition to specific diseases. With recent advances in our understanding of the genetic basis of primary open angle glaucoma (POAG), there is thus a growing possibility of developing and adapting GRS for clinical use in glaucoma.
GRS-based genetic risk estimates may aid in early disease detection, thereby allowing for timely initiation of preventive treatment and management strategies
In this paper, Fan and colleagues investigated the association of a GRS that comprised of 12 known POAG genetic risk variants with the age at diagnosis of glaucoma. The single nucleotide polymorphisms (SNPs) that were selected for construction of the GRS were the lead SNPs from the genetic loci with statistical evidence for association with POAG in European white populations. Their study comprised of a total of 3108 individuals with POAG and 3430 controls from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) study. They found that an increased load of genetic risk variants was associated with an earlier onset of disease. Affected individuals in the top 5% of the GRS had 5.2 years earlier age at diagnosis of disease compared to those in the bottom 5% GRS. The findings suggest that GRS-based genetic risk estimates may aid in early disease detection, thereby allowing for timely initiation of preventive treatment and management strategies.
The accuracy and generalizability of a GRS risk estimate is enhanced when the individual variants integrated into the GRS are from within the same population studied. Therefore, despite the presence of a larger number of genomic regions associated with POAG at a genome-wide level of significance, only the 12 European specific SNPs were selected. The clinical utility of GRS in terms of disease screening and therapeutic intervention are beginning to show promise. We look forward to future advances in improved comprehensiveness and generalizability of GRS for clinical use.