The aim of this study was to identify susceptibility variants of CACNA1A, POMP, TMEM136, AGPAT1, RBMS3, and SEMA6A genes for Exfoliation Syndrome (XFS) and Exfoliation Glaucoma (XFG) by a case-control association study approach among Georgian population. Self-reported Georgian subjects were recruited between 2015 and 2017 at a specialized ophthalmic center. Patients underwent detailed ophthalmic examination to diagnose or exclude Exfoliation Syndrome and Exfoliation Glaucoma. Patients underwent peripheral blood sampling. Genome-Wide Association Study (GWAS) was performed using Illumina OmniExpress Microarray (USA). One hundred and thirty-two XFS patients (including XFG-affected individuals) and 199 healthy subjects were included into the study. Six genes CACNA1A rs4926244, POMP rs7329408, TMEM136 rs11827818, AGPAT1 rs3130283, RBMS3 rs12490863 and SEMA6A rs10072088 variants were identified. The A alleles of SEMA6A and POMP genes are likely the risk factors of disease development in Georgians with p=0.001; OR= 1.8, 95% CI 1.2676 to 2.6973 and p=0.001; OR=1.6, 95% CI 0.9931 to 2.5634, respectively. SEMA6A homozygotes have 4 times greater risk compared to normal individuals, with p<0.004; OR=4.0, 95% CI 1.1531 to 13.9903. The G allele of CACNA1A in homozygous state increases the risk up to 3-fold with p<0.05, OR=3.15, 95% CI 0.9275 to 10.6658. The A alleles of SEMA6A and POMP increased XFG susceptibility more than 3 times (p=0.04; OR= 3.4; 95% CI: 1.2676 to 2.6973 and p=0.02; OR= 2.7; 95% CI: 0.9931 to 2.5634, respectively). Three high-risk genes have been identified in connection to XFS in Georgian population. Two genes are relevant to XFG. Three other previously described genes are not associated with the disease development.