Glaucoma is a leading cause of irreversible visual impairment and blindness worldwide. Previous genome-wide association studies have identified caveolin-1 (CAV1), ATP-binding cassette A1 (ABCA1), and forkhead box C1 (FOXC1) loci associated with primary open angle glaucoma (POAG), a major subtype of glaucoma. This study aimed to fine map the association pattern of FOXC1 locus with POAG and determine the correlations of FOXC1, ABCA1, and CAV1 variants with ocular and lipidemic parameters in southern Chinese population. In total, 1291 unrelated Han Chinese subjects were recruited, including 301 high-tension glaucoma (HTG), 126 normal-tension glaucoma (NTG), and 864 control subjects. Twelve variants in FOXC1 locus, and two variants in ABCA1 and CAV1 genes, were genotyped by TaqMan assays. Genetic risk score and genotype-phenotype correlation analyses were conducted. In the FOXC1 locus, LOC102723944 rs6596830, rather than previously reported rs2745572, showed significant association with POAG (P = 8.61 × 10, odds ratio (OR) = 0.75) and HTG (P = 3.68 × 10, OR = 0.75). ABCA1 rs2487032 was also significantly associated with POAG (P = 3.00 × 10, OR = 0.70) and HTG (P = 2.08 × 10, OR = 0.70). Joint analysis showed that carriers of homozygous non-protective alleles of ABCA1 rs2487032 and LOC102723944 rs6596830 had 2.99-fold higher risk of POAG (P = 1.27 × 10) when compared to those carrying homozygous non-risk alleles. Patients with POAG carrying ABCA1 rs2487032 G allele had higher HDL cholesterol, and those with LOC102723944 rs6596830 A allele had lower LDL. This study revealed individual and joint association of ABCA1 and LOC102723944 variants with POAG in southern Chinese population. Subjects carrying non-protective alleles had increased risk to POAG, and corresponding genotypes would affect the lipid profiles.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.