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Jie J. Wang, Elena Rochtchina, John Attia, Elizabeth G. Holliday, Wayne T. Smith, Robyn Guymer, Paul Mitchell, Blue Mountains Eye Study; A Risk Scoring System for Age-related Macular Degeneration Incorporating Genetic Susceptibility and Environmental Exposures. Invest. Ophthalmol. Vis. Sci. 2011;52(14):89.
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To develop an age-related macular degeneration (AMD) risk score system incorporating genetic susceptibility from CFH and ARMS2 genotypes and exposure to current smoking and infrequent fish consumption.
In the Blue Mountains Eye Study cohort, 3654 baseline (1992-94) participants aged 49+ years were followed-up for up to 15 years, with 65-75% of survivors re-examined at each 5-year interval. An additional 1174 Extension Study participants aged 49+ years were examined in 1999-2000. AMD lesions were assessed from retinal photographs. Cumulative (prevalent and incident) AMD cases were compared to subjects with no or hard drusen only, excluding subjects with only retinal pigment changes or distinct soft drusen. CFH (rs1061170) and ARMS2 (rs10490924) SNPswere either genotyped using Taqman assays or imputed from the 1000-genome panel based on genome-wide SNP data generated using the Illumina Human670-QuadCustom chip and after quality checking (95% typed rs1061170, 32% typed rs10490924). Six factors (two risk alleles at each of the two loci,current smoking and infrequent (<weekly) fish consumption) formed score levels from 0-4, corresponding to those with none, 1, 2, 3 or ≥4 factors. The risk magnitude (odds ratio, OR) associated with the number of co-existing factors was assessed after adjusting for age and sex.
Score levels 0 to 4 were found in 13.3, 32.7, 32.3, 17.2 and 4.5% respectively of 1308 subjects with relevant data available. Each factor had nearly equal risk magnitude for late AMD (per risk allele or smoking, OR 2.3-2.8; infrequent fish consumption, OR 1.5), justifying the use of the additive model (one score per factor). Compared to persons who scored level 0, those scoring 1, 2, 3 and 4 had increased odds of developing late (OR 3.8, 5.7, 21.6 and 23.6, respectively) or any (early or late) (OR 1.1, 1.7, 2.7 and 3.9, respectively) AMD.
A large majority of this population had at least one AMD risk factor. AMD risk increased additively as the number of risk factors increased. About 20% had 3+ risk factors and thus a high risk of AMD. Scores incorporating genes and environmental factors may help to estimate personalized AMD risk and promote efforts to modify environmental exposures.
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