Genetic Risk Score Is Associated with Vertical Cup-to-Disc Ratio and Improves Prediction of Primary Open-Angle Glaucoma in Latinos

Purpose Genome-wide association studies have identified multiple genetic variants associated with vertical cup-to-disc ratio (VCDR). Genetic risk scores (GRS) examine the aggregate genetic effect of individual variants on a trait by combining these separate genetic variants into a single measure. The purpose of this study was to construct GRS for VCDR and to determine whether the GRS are associated with VCDR and whether the GRS increase the discriminatory ability for primary open-angle glaucoma (POAG) in a Latino population. Design Population-based genetic association study. Participants A total of 4018 Latino participants recruited from Los Angeles. Methods Weighted and unweighted GRS were constructed using 68 previously reported VCDR single nucleotide polymorphisms (SNPs), as well as SNPs from our own genome-wide association data. Linear and logistic regression analyses examined the associations of GRS with VCDR and POAG, respectively. To evaluate the discriminatory ability of the GRS for POAG, we conducted receiver operating characteristic (ROC) analyses. Main Outcome Measures The relationship between GRS and VCDR in Latinos. Results The GRS were associated significantly with VCDR ( P P Conclusions To our knowledge, we identified a novel association between GRS and VCDR and its improvement in the discriminatory ability of POAG in a Latino population.