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The Contribution of Genetic Architecture to the 10-Year Incidence of Age-Related Macular Degeneration in the Fellow Eye.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2015 Aug; Vol. 56 (9), pp. 5353-61. - Publication Year :
- 2015
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Abstract
- Purpose: To correlate a genetic risk score based on age-related macular degeneration (AMD) susceptibility genes with the risk of AMD in the second eye.<br />Methods: This is a retrospective, open cohort study consisting of 891 unilateral AMD patients, who were followed for at least 12 months and recruited from three institutes. DNAs were genotyped using Illumina OmniExpress, HumanOmni2.5-8, and/or HumanExome. Survival analyses and Cox proportional hazard models were used to examine the association between 11 AMD susceptibility genes and the duration until second-eye involvement in 499 samples from Kyoto University, which were replicated in two other cohorts. Genetic risk score (GRS) was also evaluated.<br />Results: The ARMS2 rs10490924 recessive model (hazard ratio [HR]meta = 2.04; Pmeta = 3.4 × 10⁻³) and CFH rs800292 additive model (HRmeta = 1.77; Pmeta = 0.013) revealed significant associations with second-eye involvement. The dominant model of TNFRSF10A rs13278062, VEGFA rs943080, and CFI rs4698775 showed consistent effects across three datasets (I² = 0%; HRmeta = 1.46, 1.30, 1.51, respectively). The GRS using these five single nucleotide polymorphisms (SNPs) was also significantly associated (HRmeta [per score] = 2.42; P = 2.2 × 10⁻⁵; I² = 0%). After 10 years from the first visit, the patients within the top 10% by GRS showed a 51% hazard rate, in contrast to 2.3% among patients within the lowest 10% by GRS.<br />Conclusions: We demonstrated that the GRS using ARMS2, CFH, TNFRSF10A, VEGFA, and CFI was significantly associated with second-eye involvement. Genetic risk has high predictive ability for second-eye involvement of AMD.
- Subjects :
- Alleles
Complement Factor H biosynthesis
Female
Follow-Up Studies
Gene Frequency
Genetic Predisposition to Disease
Genotype
Genotyping Techniques
Humans
Incidence
Japan epidemiology
Macular Degeneration epidemiology
Macular Degeneration metabolism
Male
Phenotype
Polymorphism, Single Nucleotide
Proteins metabolism
RNA genetics
Receptors, TNF-Related Apoptosis-Inducing Ligand biosynthesis
Retrospective Studies
Risk Factors
Vascular Endothelial Growth Factor A biosynthesis
Complement Factor H genetics
Forecasting
Gene Expression Regulation
Macular Degeneration genetics
Proteins genetics
Receptors, TNF-Related Apoptosis-Inducing Ligand genetics
Vascular Endothelial Growth Factor A genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-5783
- Volume :
- 56
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 26275133
- Full Text :
- https://doi.org/10.1167/iovs.14-16020