PURPOSE. To examine the associations of the earlier reported glaucoma-related genes to the regional circumpapillary retinal nerve fiber layer thicknesses (cpRNFLTs) and corresponding visual field defects.
METHODS. We studied 756 patients with primary open-angle glaucoma (POAG) and 3094 normal controls. Each participant was genotyped for nine single nucleotide polymorphisms (SNPs) of four glaucoma-susceptible genes: the CDKN2B(AS1), TMCO1, CAV1/CAV2, and SIX1/SIX6 genes. For the SNPs that were significantly associated with the POAG case-control analyses, the associations of SNP genotypes with the cpRNFLTs of 12 sectors were also analyzed, and then finer assessments were performed using 768 points of the cpRNFLT and corresponding visual field defect sensitivities using case-only subjects.
RESULTS. We confirmed that there was a significant association of the CDKN2B(AS1) gene to POAG. For the suggested region-specific associations of these genes with the 12-sectored cpRNFLT, a 768-point cpRNFLT examination showed that rs4977756 near CDKN2B had significant signal peaks in the temporal region at 330 degrees to 360 degrees and 0 degrees to 30 degrees (maximum beta = 2.92, P = 2.9 x 10(-5) at 351.1 degrees and maximum beta = 3.97, P = 2.2 x 10(-4) at 23.4 degrees, respectively). These region-specific signals were validated by the corresponding visual field defect patterns of the paracentral/lower hemifield (P < 0.05).
CONCLUSIONS. Genetic association analyses using the cpRNFLT with 768 points suggest that the CDKN2B gene was associated with paracentral/lower hemifield scotomas. Our regional association analyses on cpRNFLT allow detailed characterization of glaucoma-related genes and should be a new target for genomic studies for glaucoma endophenotypes.