TABLE 3.
Multivariate Associations Between Individual Genetic Loci and Progression to Advanced Age-Related Macular Degeneration in the Derivation Cohort.
| Multivariate Model Ia | Multivariate Model IIb | |||
|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | |
| Genetic loci | ||||
| Complement pathway | ||||
| CFH Y402H: rs1061170 | 1.41 (1.29-1.55) | <.0001 | 1.15 (1.02-1.30) | 0.02 |
| CFH: rs1410996 | 1.68 (1.50-1.89) | <.0001 | 1.47 (1.26-1.71) | <.0001 |
| CFH R1210C: rs121913059 | 2.34 (1.43-3.80) | 0.0007 | 4.37 (2.76-6.91) | <.0001 |
| C2 E318D: rs9332739 | 0.61 (0.43-0.87) | 0.007 | 0.61 (0.43-0.87) | 0.006 |
| CFB R32Q: rs641153 | 0.58 (0.44-0.75) | <.0001 | 0.72 (0.55-0.94) | <.0001 |
| CFI: rs10033900 | 1.08 (0.99-1.18) | 0.1 | 1.06 (0.97-1.16) | 0.22 |
| C3 R102G: rs2230199 | 1.28 (1.16-1.42) | <.0001 | 1.27 (1.14-1.41) | <.0001 |
| C3 K155Q: rs147859257 | 1.84 (1.35-2.50) | 0.0001 | 1.99 (1.48-2.70) | <.0001 |
| C9 P167S: rs34882957 | 1.12 (0.81-1.55) | 0.5 | 0.92 (0.68-1.25) | 0.59 |
| CFH N1050Y: rs35274867 | 0.61 (0.36-1.05) | 0.07 | 1.17 (0.71-1.93) | 0.54 |
| Angiogenesis pathway | ||||
| VEGFA: rs943080 | 0.98 (0.89-1.08) | 0.73 | 1.01 (0.92-1.11) | 0.87 |
| TGFBR1: rs334353 | 0.95 (0.85-1.06) | 0.35 | 0.92 (0.82-1.02) | 0.1 |
| Lipid pathway | ||||
| LIPC: rs10468017 | .94 (0.84-1.04) | 0.21 | 0.96 (0.86-1.07) | 0.43 |
| ABCA1: rs1883025 | .98 (0.88-1.09) | 0.72 | 0.98 (0.88-1.10) | 0.77 |
| CETP: rs3764261 | 1.10 (1.00-1.21) | 0.04 | 1.08 (0.98-1.19) | 0.14 |
| APOC1/APOE: rs4420638 | 1.00 (0.87-1.16) | 0.99 | 0.94 (0.81-1.09) | 0.41 |
| APOH: rs1801689 | 0.74 (0.55-1.00) | 0.05 | 0.87 (0.66-1.15) | 0.32 |
| Immune/inflammatory pathway | ||||
| ARMS2/HTRA1: rs10490924 | 1.55 (1.41-1.71) | <.0001 | 1.49 (1.35-1.64) | <.0001 |
| PELI3: rs145732233 | 0.32 (0.09-1.09) | 0.07 | 0.28 (0.07-1.12) | 0.07 |
| TNFRSF10A: rs13278062 | 1.08 (0.99-1.19) | 0.09 | 1.03 (0.93-1.13) | 0.61 |
| SLC16A8: rs8135665 | 1.05 (0.94-1.18) | 0.4 | 1.06 (0.95-1.19) | 0.28 |
| PILRB/PILRA: rs11769700 | 1.05 (0.94-1.17) | 0.42 | 1.04 (0.93-1.16) | 0.49 |
| TMEM97/VTN: rs704 | 0.98 (0.89-1.08) | 0.69 | 0.92 (0.84-1.02) | 0.1 |
| Extracellular matrix | ||||
| COL8A1: rs13095226 | 1.22 (1.06-1.41) | 0.005 | 1.18 (1.02-1.37) | 0.03 |
| COL4A3: rs11884770 | 0.95 (0.86-1.06) | 0.34 | 0.95 (0.86-1.06) | 0.36 |
| CTRB1: rs8056814 | 0.79 (0.65-0.96) | 0.02 | 0.85 (0.70-1.03) | 0.1 |
| ADAMTS9: rs6795735 | 0.98 (0.89-1.08) | 0.64 | 1.01 (0.92-1.11) | 0.86 |
| TIMP3: rs9621532 | 0.74 (0.58-0.94) | 0.02 | 0.81 (0.63-1.04) | 0.09 |
| DNA repair/protein binding | ||||
| RAD51B: rs8017304 | 0.86 (0.77-0.95) | 0.003 | 0.85 (0.77-0.95) | 0.003 |
| NPLOC4/TSPAN10: rs9895741 | 1.08 (0.98-1.19) | 0.1 | 1.06 (0.96-1.16) | 0.26 |
| HSPH1/B3GALTL: rs9542236 | 1.17 (1.07-1.29) | 0.0005 | 1.14 (1.04-1.25) | 0.005 |
AMD = age-related macular degeneration; CI = confidence interval; HR = hazard ratio.
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, adjusted for age, sex, race, education, baseline AMD grade, BMI, smoking status, and all other genetic loci in the table.