Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables
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PURPOSE: The joint effects of genetic, ocular, and environmental variables were evaluated and predictive models for prevalence and incidence of AMD were assessed. METHODS: Participants in the multicenter Age-Related Eye Disease Study (AREDS) were included in a prospective evaluation of 1446 individuals, of which 279 progressed to advanced AMD (geographic atrophy or neovascular disease) and 1167 did not progress during 6.3 years of follow-up. For prevalent AMD, 509 advanced cases were compared with 222 controls. Covariates for the incidence analysis included age, sex, education, smoking, body mass index (BMI), baseline AMD grade, and the AREDS vitamin-mineral treatment assignment. DNA specimens were evaluated for six variants in five genes related to AMD. Unconditional logistic regression analyses were performed for prevalent and incident advanced AMD. An algorithm was developed and receiver operating characteristic curves and C statistics were calculated to assess the predictive ability of risk scores to discriminate progressors from nonprogressors. RESULTS: All genetic polymorphisms were independently related to prevalence of advanced AMD, controlling for genetic factors, smoking, BMI, and AREDS treatment. Multivariate odds ratios (ORs) were 3.5 (95% confidence interval [CI], 1.7-7.1) for CFH Y402H; 3.7 (95% CI, 1.6-8.4) for CFH rs1410996; 25.4 (95% CI, 8.6-75.1) for LOC387715 A69S (ARMS2); 0.3 (95% CI, 0.1-0.7) for C2 E318D; 0.3 (95% CI, 0.1-0.5) for CFB; and 3.6 (95% CI, 1.4-9.4) for C3 R102G, comparing the homozygous risk/protective genotypes to the referent genotypes. For incident AMD, all these variants except CFB were significantly related to progression to advanced AMD, after controlling for baseline AMD grade and other factors, with ORs from 1.8 to 4.0 for presence of two risk alleles and 0.4 for the protective allele. An interaction was seen between CFH402H and treatment, after controlling for all genotypes. Smoking was independently related to AMD, with a multiplicative joint effect with genotype on AMD risk. The C statistic for the full model with all variables was 0.831 for progression to advanced AMD. CONCLUSIONS: Factors reflective of nature and nurture are independently related to prevalence and incidence of advanced AMD, with excellent predictive power.
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Because the prediction model included only genetic risk factors, the performance of advanced AMD risk assessment is expected to improve with additional environmental and demographic factors in prospective studies.
“As this prediction model only included genetic risk factors, we expect an improvement of the performance of advanced AMD risk assessment with additional environmental and demographic factors in prospective studies as in our previous calculations (18,19).”
From Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration (2011) · cites this paper as [19]
A combined risk score including multiple genetic loci along with demographic, environmental and macular characteristics which modify risk is highly predictive of progression from early and intermediate stages of AMD to advanced stages which cause visual loss.
“A combined risk score including these multiple genetic loci along with demographic, environmental and macular characteristics which modify risk is highly predictive of progression from the early and intermediate stages of AMD to the advanced stages which cause visual loss (18,19).”
From Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration (2011) · cites this paper as [19]
Combined with demographic, ocular, and environmental factors, these loci have potential predictive power.
“and combined with demographic, ocular, and environmental factors, they have potential predictive power ([14](#r14))”
From Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene ( <i>LIPC</i> ) (2010) · cites this paper as [14]
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- Authors
- Seddon, J. M., Reynolds, R., Maller, J., Fagerness, J. A., Daly, M. J., & Rosner, B.
- Affiliations
- Tufts University (US)
- Broad Institute (US)
- Harvard University (US)
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2009-05-01
- Volume
- 50
- Issue
- 5
- Pages
- 2044
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC3772781
- OpenAlex
- W2020256864
- Cited by
- 285
- References
- 42
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 4 · 2023: 4 · 2022: 12 · 2021: 6 · 2020: 6 · 2019: 8 · 2018: 9 · 2017: 15 · 2016: 14 · 2015: 23 · 2014: 23 · 2013: 26 · 2012: 41
- FWCI
- 40.31
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Tufts Medical Center
- National Institutes of Health (6u54rr020278-06)
- National Eye Institute (R01 EY 11309, R01EY011309)
- National Center for Research Resources (U54-RR020278)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- advanced age-related macular degeneration, geographic atrophy, neovascular AMD, genetic polymorphism, ARMS2, CFB, AMD progression, risk score prediction model, smoking, body mass index, genetic risk factors, AREDS
- MeSH terms
- Aged, Algorithms, Complement C2, Complement C3, Environment, Female, Genotype, Humans, Macular Degeneration, Male, Models, Genetic, Phenotype, Polymorphism, Genetic, Complement Factor B, Prospective Studies, Proteins, Risk Factors, ROC Curve, Incidence, Prevalence, Complement Factor H, Molecular Epidemiology, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Polymorphism, Single Nucleotide
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