The allele frequencies of the 23 tSNPs among the three separate case groups (HTG, NTG, OHT) and controls were assessed; tSNPs showing significant effects are shown in
Table 2 .
In the HTG group, four tSNPs (all situated in intron 2) had allele frequencies that differed significantly between patients and controls. Protective allele frequencies of rs7859156, rs6478750, and rs7854658 were higher in controls than in HTG patients (P = 0.0015, 0.0258, and 0.0057, respectively), with ORs of 0.64, 0.72, and 0.65, respectively, after adjustment for sex. By contrast, the risk allele frequency of rs10987385 was higher in the HTG patients than in controls (P = 0.0180), with an OR of 1.43 after adjustment for sex.
In the OHT group, two of these tSNPs (both situated in intron 2) had allele frequencies that differed significantly between patients and controls. Protective allele frequencies of rs7859156 and rs6478750 were higher in controls than in OHT patients (P = 0.0482 and P = 0.0309, respectively), both with ORs of 0.59 after adjustment for age.
In the NTG group, five tSNPs had allele frequencies that differed significantly between NTG patients and controls, but only one of these alleles (rs7854658) was in common with the significant HTG tSNPs. The protective allele frequency of rs7854658 was higher in the controls than in NTG patients (P = 0.0041) with an OR of 0.30. In addition, risk allele frequencies of rs944103, rs16929236, rs10733682, and rs867559 were higher in NTG patients than in controls (P = 0.0488, 0.0064, 0.0489, and 0.0295, respectively), with ORs of 1.71, 2.30, 1.75, or 1.82, respectively, after adjustment for sex. rs7854658 and rs944103 are situated in intron 2, whereas rs16929236, rs10733682, and rs867559 are situated in the 3′ region of LMX1B. After permutation testing, all P values for these differences between patients in each group and controls increased beyond the significant level of 0.05, except for rs7859156, which had a permutated P value of 0.0376 after 1000 tests in the HTG group.
Next, we tested the allele frequencies of the 23 tSNPs in the combined groups of all patients with raised IOP (HTG and OHT), or all patients with glaucomatous optic neuropathy—that is, all the POAG patients (HTG and NTG), compared with the control group. In both groups, HTG+OHT and HTG+NTG, the same four tSNPs had an allele frequency that differed significantly between patients and controls
(Table 2) . Protective allele frequencies of rs7859156, rs6478750, and rs7854658 were higher in controls than cases, and risk allele frequencies of rs10987385 were higher in patients than in controls. In both combined groups, tSNP rs7859156, remained significantly different after 1000 permutation tests (
P < 0.05). In addition, in the combined POAG case group (HTG+NTG), a second tSNP rs7854658 remained significantly different after permutation testing.