ny genes and environmental factors contribute to the disease, similar to heart disease, schizophrenia and diabetes. The combinations of variation within a given gene and between genes, along with environmental factors, confers one's lifetime risk of a disease like AMD. Variations in the BF/C2 gene are protective for AMD, whereas the more common variations in the other two genes, CFH and LOC, increase risk of AMD. The authors provide new calculations that one's lifetime risk of AMD ranges from less than 1% to more than 50%, depending on the variations one has in these three genes. The research team also showed that the three genes do not interact, but confer risk independently.

AMD is the leading cause of irreversible visual impairment and blindness among persons aged 60 and older. With the elderly population steadily growing, the burden related to this loss of visual function will increase. Limited treatment options exist and prevention remains the best approach for addressing this public health concern.

"The overall implication of this study is that depending on your genotype related to these five variants in three genes, and most likely more to be discovered, preventive and therapeutic drug targets may be better designed and tailored to an individual's need, ie., personalized medicine," said Dr. Seddon.

This study evaluated a large number of samples from individuals with advanced AMD, including both geographic atrophy or "dry" AMD, and neovascular disease or "wet" AMD, which cause visual loss. It is noteworthy that no differences were found between these subtypes of advanced AMD with respect to the variations found in the genes.

Dr. Seddon and her colleagues previously reported that the heritability of AMD is high (46% to 71%) in a large US cohort of elderly twins (Arch Ophthalmol 2005), and that another common CFH variant as well as smoking and higher body mass index are independently related to advanced AMD (Human Her
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Contact: Mary Leach
mary_leach@meei.harvard.edu
617-573-4170
Harvard Medical School
29-Aug-2006

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