Assessment of polygenic effects links primary open-angle glaucoma and age-related macular degeneration

Primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD) are leading causes of irreversible blindness. Several loci have been mapped using genome-wide association studies. Until very recently, there was no recognized overlap in the genetic contribution to AMD and POAG. At genome-wide significance level, only ABCA1 harbors associations to both diseases. Here, we investigated the genetic architecture of POAG and AMD using genome-wide array data. We estimated the heritability for POAG (h(2)(g) = 0.42 ± 0.09) and AMD (h(2)(g) = 0.71 ± 0.08). Removing known loci for POAG and AMD decreased the h(2)(g) estimates to 0.36 and 0.24, respectively. There was evidence for a positive genetic correlation between POAG and AMD (r(g) = 0.47 ± 0.25) which remained after removing known loci (r(g) = 0.64 ± 0.31). We also found that the genetic correlation between sexes for POAG was likely to be less than 1 (r(g) = 0.33 ± 0.24), suggesting that differences of prevalence among genders may be partly due to heritable factors.