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D. D. Despriet, C. M. van Duijn, P. T. V. M. de Jong, J. R. Vingerling, A. A. B. Bergen, C. C. W. Klaver; Genetic Diagnosis of Age-RMacular Degeneration: The Role of Molecular Genetics in the Identification of High Risk Eyes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1769.
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Five genes have been highly associated with age-related macular degeneration (AMD): Complement Factor H, LOC387715/HTRA1, Complement component C3, Complement component C2, and Factor B. We calculated the predictive value of multiple genetic testing to assess whether genetic testing will be useful for clinical practice.
We investigated these genes in three different settings: the population-based Rotterdam Study, a case-control study, and a study from a genetic isolate. The analyses were based on 4871 persons with no AMD, 653 with early AMD, and 460 with late AMD.
All risk alleles were independently associated with AMD in a multivariate analysis including age, sex and smoking, except for alleles from C3. The predictive value of genetic testing (86%) exceeded that of age and smoking (77%) in a model that included all subjects, indicating that multiple genetic testing can be used to discriminate those who will develop late AMD from those who will not in a general population. The predictive value of genetic testing (72%) also exceeded that of age and smoking (61%) in a model including late AMD and older subjects with early AMD, signifying that genetic testing helps to distinguish those who will progress to late AMD from those who will remain stable. Absolute risks of late AMD by age 80 yrs altered after testing to 60% for persons homozygous for high risk alleles, and to <1% for persons carrying no risk alleles.
Multiple genetic testing has a high predictive value for late AMD. Testing can already be helpful for current clinical practice in counseling patients. It will become even more beneficial when protective therapies become available.
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