1. Oct 24, 2019

Genetic Risk Scores With POAG Risk Variants Associated With Age at Diagnosis

A new study in JAMA Ophthalmology investigated if genetic risk scores comprising 12 primary open-angle glaucoma (POAG) risk variants were associated with age at diagnosis. Genetic variants influence disease risk but clinical effects of associated variants is unknown.

The cross-sectional study included patients with POAG and controls from the Glaucoma Genes and Environment (GLAUGEN) study (976 individuals with POAG and 1,140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) study (2,132 individuals with POAG and 2,290 controls). A genetic risk score was calculated using 12 variants associated with POAG. Mean (SD) age at diagnosis for individuals with POAG was 63.6 (9.8) years in the GLAUGEN cohort and 66.0 (13.7) years in the NEIGHBOR cohort. Mean (SD) age at enrollment for controls was 65.5 (9.2) years in the GLAUGEN cohort and 68.9 (11.4) years in the NEIGHBOR cohort.

Results showed that the genetic risk score was strongly associated with POAG risk in case-control analysis (odds ratio per 1-point increase in score = 1.24; 95% CI, 1.21-1.27; P = 3.4 × 10−66). In case-only analyses, each higher genetic risk score unit was associated with a 0.36-year earlier age at diagnosis (β = −0.36; 95% CI, −0.56 to −0.16; P = 4.0 × 10−4). Higher doses of POAG risk alleles were associated with earlier age at diagnosis, and those with POAG with the highest genetic risk score had 5.2-year earlier age at diagnosis.

Based on these results, genetic risk scores comprising genetic variants associated with POAG could help identify patients at risk of earlier disease onset.


Fan BJ, Bailey JC, Igo RP Jr., et al. Association of a primary open-angle glaucoma genetic risk score with earlier age at diagnosis. JAMA Ophthalmol. 2019;137(10):1190-1194. doi:10.1001/jamaophthalmol.2019.3109.