Variation in 3 genes influences risk of age-related macular degeneration

BOSTON (Aug. 29, 2006) -- Researchers in Boston have discovered a new common, noncoding variant in the Complement Factor H (CFH) gene that is associated with age-related macular degeneration (AMD), the leading cause of irreversible visual impairment and blindness among persons aged 60 and older. Their analyses, for the first time, combine this new variant with all previously reported variants to estimate individual risk of advanced AMD. They observed additive accumulation of risk from alleles at these three genes, including CFH on chromosome 1, complement factor B (BF) and complement component 2 (C2) genes on chromosome 6, and the LOC gene on chromosome 10. They estimate that genotypes related to five variants in these three genes explain about half the sibling risk of AMD in the study population. Results are published online in Nature Genetics.

The principal investigator, Johanna M. Seddon, M.D., Director of the Epidemiology Unit and Macular Degeneration specialist at the Massachusetts Eye and Ear Infirmary, and Associate Professor at Harvard Medical School, collaborated with co-authors from the Center for Human Genetic Research at Massachusetts General Hospital and the Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology. They studied 2,172 unrelated European-descended individuals 60 years of age or older, who were diagnosed on the basis of ocular examination and ocular photography (1,238 affected individuals and 934 controls). Affected individuals were defined as those having advanced AMD related to visual loss with either geographic atrophy (dry) or neovascular (wet) disease. Controls were individuals without AMD. The mean age was 74 for controls (54% female) and 78 years for affected individuals (55% female). Both Illumina and Sequenom methods were used to genotype about 1540 single nucleotide polymorphisms (snp's).

AMD is a "common disease" meaning that it is complex, i.e., ma

Contact: Mary Leach
Harvard Medical School

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