Author(s): Joachim N, Kifley A, Colijn JM, Lee KE, Buitendijk GHS, Klein BEK, Myers C, Meuer SM, Tan AG, Flood V, Schoufour JD, Franco OH, Holliday EG, Attia J, Liew G, Iyengar SK, de Jong PTVM, Hofman A, Vingerling JR, Mitchell P, Klein R, Klaver CCW, Wang JJ. Joint Contribution of Genetic Susceptibility and Modifiable Factors to the Progression of Age-Related Macular Degeneration over 10 Years: The Three Continent AMD Consortium Report. Ophthalmol Retina. 2018 Jul;2(7):684-693. doi: 10.1016/j.oret.2017.10.019. Epub 2017 Dec 30.
PURPOSE To assess joint effects of genetic and modifiable factors on the 10-year progression of age-related macular degeneration (AMD).
DESIGN Individual and pooled data analyses of 2 population-based cohorts.
PARTICIPANTS Blue Mountains Eye Study (BMES) and Rotterdam Study (RS) participants (n = 835).
METHODS Participants of the BMES and RS were followed up over 10 years or more. At baseline and follow-up visits, interviews using questionnaires and eye examinations with retinal photography were performed. Age-related macular degeneration was assessed by trained photographic graders and verified by retinal specialists. Genetic susceptibility to AMD meant carrying 2 or more risk alleles of the CFH or ARMS2 SNPs, or both (rs1061170 and rs10490924), relative to 0 or 1 risk allele. Discrete logistic regression models were used to investigate the joint associations of genetic susceptibility and either smoking, fish consumption, dietary intake of lutein-zeaxanthin, or combined environmental risk scores from the 3 modifiable factors with the risk of AMD progression. Odds ratios (ORs) with 95% confidence intervals (CIs) and synergy indexes are reported.
MAIN OUTCOME MEASURE Ten-year progression of AMD, categorized as any (≥1 step) or 2-step (≥2 steps) progression on the Three Continent AMD Consortium 5-step severity scale.
RESULTS Older age, the presence of AMD genetic susceptibility, and baseline AMD status were associated strongly with AMD progression (P < 0.0001). In analyses of pooled data, each additional score from the combined environmental risk scores was associated with an increased risk of 2-step progression over 10 years (OR, 1.26; 95% CI, 1.02-1.56). The copresence of AMD genetic susceptibility and combined risk score of 3 or more was associated with a substantially higher risk of 2-step progression compared with the presence of either factor alone. There was a significant synergistic effect (OR, 4.14; 95% CI, 1.07-15.95) and interaction (P = 0.025) between genetic susceptibility and environmental risk score of 3 or more.
CONCLUSIONS Among persons with AMD genetic susceptibility and pre-existing early AMD lesions, presenting with high environmental risk scores from 3 modifiable factors (smoking, infrequent consumption of fish, low lutein-zeaxanthin intake) were associated with an increased risk of 2-step progression over 10 years.