Purpose To evaluate the independent and joint effects of genetic factors and environmental variables on
advanced forms of age related macular degeneration (AMD) including geographic atrophy (GA) and choroidal
neovascularization (CNV), and to develop a predictive model with both genetic and environmental factors
included.
Methods Demographic information, including age of onset, smoking status and body mass index (BMI), was
collected in 1844 participants. Genotypes were evaluated for eight variants in five genes related to AMD.
Unconditional logistic regression analyses were performed to generate a risk predictive model.
Results All genetic variants showed strong association with AMD. Multivariate odds ratios (ORs) were 3.52
(95% CI: 2.08-5.94) for CFH rs1061170 CC, 4.21 (95% CI: 2.30-7.70) for CFH rs2274700 CC, 0.46 (95%
CI:0.27-0.80) for C2 rs9332739 CC/CG, 0.44 (95% CI: 0.30-0.66) for CFB rs641153 TT/CT, 10.99 (95% CI:
6.04-19.97) for HTRA1/LOC387715 rs10490924 TT and 2.66 (95% CI: 1.43-4.96) for C3 rs2230199 GG.
Smoking was independently associated with advanced AMD after controlling for age, gender, BMI and all
genetic variants.
Conclusions CFH confers more risk to the bilaterality of GA whereas LOC387715/HTRA1 contributes more to
the bilaterality of CNV. C3 confers more risk for GA than CNV. Risk models with combined genetic and
environmental factors together have notable discrimination power. Early detection and risk prediction of AMD
could help to improve the prognosis of AMD and reduce the outcome of blindness. Targeting high risk
individuals for surveillance and clinical interventions may help reduce disease burden.