TABLE 4.
Multivariate Associations Between Individual Genetic Loci and Progression to Geographic Atrophy and Neovascular Disease Subtypes in the Derivation Cohort.
| GA | NV | |||||||
|---|---|---|---|---|---|---|---|---|
| Multivariate Model Ia | Multivariate Model IIb | Multivariate Model Ia | Multivariate Model IIb | |||||
| HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | |
| Genetic loci | ||||||||
| Complement pathway | ||||||||
| CFH Y402H: rs1061170 | 1.47 (1.29-1.67) | <.0001 | 1.05 (0.86-1.28) | 0.63 | 1.53 (1.36-1.72) | <.0001 | 1.17 (1.00-1.35) | 0.04 |
| CFH: rs1410996 | 1.76 (1.50-2.06) | <.0001 | 1.45 (1.14-1.85) | 0.003 | 1.87 (1.62-2.17) | <.0001 | 1.45 (1.19-1.76) | 0.0002 |
| CFH R1210C: rs121913059 | 2.84 (1.34-6.03) | <.0001 | 3.94 (1.90-8.15) | 0.001 | 2.66 (1.45-4.88) | 0.002 | 4.25 (2.05-8.79) | <.0001 |
| C2 E318D: rs9332739 | 0.45 (0.26-0.80) | 0.006 | 0.64 (0.34-1.21) | 0.17 | 0.66 (0.43-1.02) | 0.06 | 0.72 (0.48-1.10) | 0.13 |
| CFB R32Q: rs641153 | 0.53 (0.37-0.77) | 0.0007 | 0.74 (0.48-1.12) | 0.16 | 0.53 (0.37-0.75) | 0.0003 | 0.73 (0.52-1.03) | 0.07 |
| CFI: rs10033900 | 1.13 (0.99-1.29) | 0.08 | 1.14 (0.97-1.32) | 0.1 | 1.08 (0.96-1.21) | 0.2 | 1.00 (0.90-1.12) | 0.97 |
| C3 R102G: rs2230199 | 1.30 (1.12-1.50) | 0.0005 | 1.16 (0.98-1.39) | 0.09 | 1.34 (1.18-1.53) | <.0001 | 1.25 (1.09-1.42) | 0.001 |
| C3 K155Q: rs147859257 | 2.21 (1.49-3.28) | <.0001 | 2.59 (1.64-4.08) | <.0001 | 1.72 (1.08-2.73) | 0.02 | 1.24 (0.75-2.04) | 0.4 |
| C9 P167S: rs34882957 | 1.27 (0.80-2.01) | 0.32 | 0.87 (0.53-1.43) | 0.4 | 1.08 (0.71-1.63) | 0.73 | 0.83 (0.54-1.30) | 0.42 |
| CFH N1050Y: rs35274867 | 0.57 (0.26-1.25) | 0.16 | 0.94 (0.32-2.78) | 0.91 | 0.59 (0.28-1.23) | 0.16 | 1.26 (0.62-2.58) | 0.53 |
| Angiogenesis pathway | ||||||||
| VEGFA: rs943080 | 0.97 (0.85-1.11) | 0.64 | 0.98 (0.84-1.14) | 0.76 | 1.01 (0.90-1.14) | 0.85 | 1.07 (0.94-1.21) | 0.3 |
| TGFBR1: rs334353 | 1.03 (0.89-1.20) | 0.68 | 0.98 (0.82-1.17) | 0.79 | 0.89 (0.77-1.03) | 0.11 | 0.83 (0.72-0.96) | 0.01 |
| Lipid pathway | ||||||||
| LIPC: rs10468017 | 0.88 (0.76-1.02) | 0.09 | 0.90 (0.75-1.08) | 0.26 | 0.97 (0.85-1.10) | 0.63 | 1.02 (0.89-1.16) | 0.83 |
| ABCA1: rs1883025 | 0.97 (0.83-1.13) | 0.7 | 1.05 (0.88-1.26) | 0.58 | 0.95 (0.83-1.09) | 0.45 | 0.95 (0.83-1.10) | 0.51 |
| CETP: rs3764261 | 1.09 (0.96-1.24) | 0.2 | 1.02 (0.87-1.20) | 0.78 | 1.14 (1.01-1.29) | 0.03 | 1.08 (0.96-1.23) | 0.21 |
| APOC1/APOE: rs4420638 | 1.03 (0.84-1.27) | 0.77 | 0.98 (0.77-1.25) | 0.88 | 1.00 (0.83-1.20) | 1 | 0.93 (0.78-1.12) | 0.46 |
| APOH: rs1801689 | 0.62 (0.41-0.95) | 0.03 | 0.93 (0.60-1.44) | 0.74 | 0.72 (0.49-1.06) | 0.1 | 0.88 (0.58-1.34) | 0.56 |
| Genetic loci | ||||||||
| Immune/inflammatory pathway | ||||||||
| ARMS2/HTRA1: rs10490924 | 1.59 (1.39-1.81) | <.0001 | 1.42 (1.21-1.65) | <.0001 | 1.75 (1.55-1.97) | <.0001 | 1.57 (1.39-1.78) | <.0001 |
| PELI3: rs145732233 | 0.21 (0.04-1.22) | 0.08 | 0.26 (0.03-2.01) | 0.2 | 0.34 (0.06-1.96) | 0.23 | 0.39 (0.06-2.51) | 0.32 |
| TNFRSF10A: rs13278062 | 1.17 (1.02-1.33) | 0.03 | 1.12 (0.95-1.31) | 0.18 | 1.04 (0.92-1.17) | 0.55 | 0.92 (0.82-1.04) | 0.2 |
| SLC16A8: rs8135665 | 1.08 (0.92-1.26) | 0.35 | 1.11 (0.92-1.34) | 0.29 | 1.03 (0.89-1.19) | 0.69 | 1.01 (0.88-1.17) | 0.89 |
| PILRB/PILRA: rs11769700 | 1.03 (0.87-1.21) | 0.75 | 0.97 (0.79-1.19) | 0.78 | 1.10 (0.96-1.27) | 0.18 | 1.13 (0.98-1.31) | 0.09 |
| TMEM97/VTN: rs704 | 0.99 (0.86-1.13) | 0.82 | 1.06 (0.85-1.34) | 0.6 | 0.97 (0.86-1.09) | 0.59 | 0.94 (0.83-1.07) | 0.35 |
| Extracellular matrix | ||||||||
| COL8A1: rs13095226 | 1.34 (1.09-1.64) | 0.006 | 1.26 (0.98-1.61) | 0.07 | 1.24 (1.04-1.48) | 0.02 | 1.18 (0.99-1.41) | 0.07 |
| COL4A3: rs11884770 | 1.04 (0.89-1.20) | 0.65 | 1.13 (0.95-1.34) | 0.16 | .089 (0.78-1.01) | 0.07 | 0.86 (0.75-0.98) | 0.03 |
| CTRB1: rs8056814 | 0.79 (0.60-1.04) | 0.09 | 0.88 (0.65-1.19) | 0.4 | 0.74 (0.58-0.95) | 0.02 | 0.83 (0.65-1.06) | 0.14 |
| ADAMTS9: rs6795735 | 0.34 (0.82-1.07) | 0.34 | 0.90 (0.77-1.05.05) | 0.19 | 1.02 (0.90-1.15) | 0.8 | 1.08 (0.96-1.21) | 0.22 |
| TIMP3: rs9621532 | 0.71 (0.51-0.99) | 0.04 | 0.82 (0.56-1.19) | 0.3 | 0.66 (0.47-0.93) | 0.02 | 0.75 (0.53-1.06) | 0.1 |
| DNA repair/protein binding | ||||||||
| RAD51B: rs8017304 | 0.87 (0.76-1.01) | 0.06 | 0.97 (0.82-1.15) | 0.71 | 0.81 (0.72-0.92) | 0.002 | 0.81 (0.71-0.92) | 0.002 |
| NPLOC4/TSPAN10: rs9895741 | 1.06 (0.92-1.22) | 0.39 | 1.01 (0.86-1.19) | 0.89 | 1.13 (1.00-1.28) | 0.05 | 1.11 (0.99-1.25) | 0.08 |
| HSPH1/B3GALTL: rs9542236 | 1.19 (1.05-1.35) | 0.008 | 1.08 (0.93-1.26) | 0.29 | 1.23 (1.09-1.38) | 0.0007 | 1.12 (0.99-1.26) | 0.08 |
AMD = age-related macular degeneration; CI = confidence interval; GA = geographic atrophy; HR = hazard ratio; NV = neovascular disease.
a
Multivariate Model I: HRs for 12 year progression, risk per allele, adjusted for age, sex, race, education, and baseline AMD grade.
b
Multivariate Model II: HRs reflect risk per allele, and are adjusted for age, sex, race, education, baseline AMD grade, BMI, smoking status, and all other genetic loci in the Table.