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Letter

Nature Genetics 38, 1055–1059 (1 September 2006) | doi:10.1038/ng1873

Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration

Julian Maller , Sarah George , Shaun Purcell , Jes Fagerness , David Altshuler , Mark J Daly & Johanna M Seddon

Age-related macular degeneration (AMD) is a common, late-onset disease with seemingly typical complexity: recurrence ratios for siblings of an affected individual are three- to sixfold higher than in the general population, and family-based analysis has resulted in only modestly significant evidence for linkage. In a case-control study drawn from a US-based population of European descent, we have identified a previously unrecognized common, noncoding variant in CFH, the gene encoding complement factor H, that substantially increases the influence of this locus on AMD, and we have strongly replicated the associations of four other previously reported common alleles in three genes (P values ranging from 10|[minus]|6 to 10|[minus]|70).