Table 5.
Multivariable odds ratio (95% Confidence Intervals; p-value) for dichotomous glaucoma-related variables associated with each increase in minor allele of cyclin dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2BAS) single nucleotide polymorphisms (SNPs)
| LD Block 1 | LD Block 2 | LD Block 3 | LD Block 4 | LD Block 5 | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| rs3217992 | rs1063192 | rs573687 | rs7049105 | rs2157719 | rs2151280 | rs1412829 | rs1012068 | rs4977756 | rs1412832 | |
| History of IOP >21 mm Hg | 0.72 (0.58, 0.90) p=0.004 |
1.39 (1.17, 1.66) p=2.00E-04 |
1.48 (1.26, 1.74) p=2.12E-06 |
1.38 (1.08, 1.77) p=0.01 |
1.48 (1.19, 1.83) p=4.00E-04 |
1.40 (1.10, 1.78) p=0.01 |
1.44 (1.19, 1.73) p=2.00E-04 |
1.38 (1.08, 1.76) p=0.01 |
1.39 (1.04, 1.84) p=0.02 |
1.36 (1.06, 1.76) p=0.02 |
| CDR >0.6 at diagnosis | 1.44 (1.07, 1.94) p=0.02 |
0.71 (0.53, 0.95) p=0.02 |
0.68 (0.50, 0.92) p=0.01 |
0.74 (0.56, 0.98) p=0.04 |
0.71 (0.53, 0.95) p=0.02 |
0.72 (0.54, 0.95) p=0.02 |
0.71 (0.53, 0.96) p=0.02 |
0.71 (0.54, 0.94) p=0.02 |
0.63 (0.47, 0.86) p=0.003 |
0.65 (0.48, 0.90) p=0.01 |
| CDR>0.6 at DNA collection | 1.43 (1.04, 1.97) p=0.03 |
0.71 (0.52, 0.98) p=0.03 |
0.81 (0.58, 1.13) p=0.22 |
0.68 (0.50, 0.92) p=0.01 |
0.73 (0.53, 1.00) p=0.05 |
0.68 (0.50, 0.92) p=0.01 |
0.74 (0.54, 1.01) p=0.06 |
0.75 (0.55, 1.02) p=0.06 |
0.68 (0.49, 0.94) p=0.02 |
0.75 (0.53, 1.05) p=0.09 |
| Filtration surgery | 1.14 (0.88, 1.46) p=0.33 |
0.91 (0.69, 1.19) p=0.48 |
1.02 (0.77, 1.36) p=0.88 |
0.80 (0.62, 1.03) p=0.09 |
0.90 (0.68, 1.18) p=0.44 |
0.82 (0.64, 1.06) p=0.13 |
0.93 (0.71, 1.23) p=0.62 |
0.85 (0.66, 1.11) p=0.23 |
0.91 (0.69, 1.21) p=0.54 |
0.75 (0.55, 1.04) p=0.09 |
| Peripheral only visual field loss | 0.79 (0.70, 0.89) p=1.00E-04 |
1.23 (1.09, 1.40) p=0.002 |
1.15 (1.01, 1.31) p=0.04 |
1.21 (1.01, 1.45) p=0.04 |
1.24 (1.09, 1.41) p=9.00E-04 |
1.22 (1.03, 1.45) p=0.02 |
1.23 (1.08, 1.40) p=0.002 |
1.19 (0.94, 1.50) p=0.14 |
1.17 (1.03, 1.34) p=0.02 |
1.19 (1.03, 1.37) p=0.02 |
| Paracentral only visual field loss | 0.91 (0.73, 1.13) p=0.39 |
0.97 (0.76, 1.23) p=0.79 |
1.13 (0.80, 1.60) p=0.48 |
1.12 (0.9, 1.39) p=0.29 |
1.01 (0.77, 1.32) p=0.94 |
1.11 (0.90, 1.38) p=0.31 |
1.00 (0.80, 1.25) p=0.99 |
1.14 (0.92, 1.41) p=0.22 |
1.03 (0.82, 1.29) p=0.80 |
1.00 (0.62, 1.61) p=0.99 |
| Superior only visual field loss | 1.03 (0.89, 1.20) p=0.71 |
0.9 (0.79, 1.03) p=0.12 |
0.96 (0.84, 1.11) p=0.60 |
0.93 (0.74, 1.18) p=0.58 |
0.90 (0.79, 1.03) p=0.14 |
0.95 (0.77, 1.18) p=0.67 |
0.92 (0.81, 1.05) p=0.23 |
0.95 (0.8, 1.12) p=0.53 |
0.91 (0.80, 1.05) p=0.20 |
0.88 (0.76, 1.02) p=0.10 |
| Inferior only visual field loss | 0.87 (0.76, 0.99) p=0.03 |
1.23 (1.07, 1.42) p=0.003 |
1.19 (1.03, 1.37) p=0.02 |
1.17 (1.02, 1.35) p=0.02 |
1.23 (1.07, 1.42) p=0.004 |
1.14 (1.00, 1.30) p=0.05 |
1.2 (1.04, 1.38) p=0.01 |
1.12 (0.98, 1.28) p=0.09 |
1.19 (1.04, 1.38) p=0.02 |
1.15 (0.99, 1.35) p=0.07 |
Significance and effect sizes of associations of CDKN2BAS region SNPs after meta-analysis of Glaucoma Genes and Environment (GLAUGEN) and National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) cases using logistic regression on various outcome variables. Significant p values are in bold. We used a Bonferroni corrected statistical significance level of 0.001 (0.05/((5 representative SNPs)*(10 outcome variables))). No models had a p for heterogeneity <0.05. GLAUGEN regression models controlled for age of diagnosis, deoxyribonucleic acid (DNA) specimen source (blood or cheek), gender, site, method of DNA extraction, and three eigenvectors, and NEIGHBOR regression models controlled for age of diagnosis, DNA specimen source (blood or cheek), gender, site, and two eigenvectors.
Abbreviations used: IOP=intraocular pressure; CDR=cup-disc ratio.
Age at diagnosis is in years. IOP data is in mm Hg. LD= linkage disequilibrium
NB: Certain phenotype features were absent on some subsets of GLAUGEN and NEIGHBOR. We included data on filtration surgery from GLAUGEN only as it was absent from all NEIGHBOR sites except the Collaborative Intervention Glaucoma Treatment Study (CIGTS) and Advanced Glaucoma Intervention Study sub sites of NEIGHBOR. In the latter subsets, filtration surgery was performed as part of randomized trials and thus this data was excluded. We included data on CDR >0.6 at diagnosis from the Nurses Health Study (NHS) and Health Professionals Follow-up Study (HPFS) subsets of GLAUGEN. We included data on CDR>0.6 at DNA collection from the Mass Eye and Ear Infirmary (MEEI) subset of GLAUGEN and all NEIGHBOR sites.