2013-11-01
Identification of a rare coding variant in complement 3 associated with age-related macular degeneration
Publication
Publication
Nature Genetics , Volume 45 - Issue 11 p. 1375- 1381
Macular degeneration is a common cause of blindness in the elderly. To identify rare coding variants associated with a large increase in risk of age-related macular degeneration (AMD), we sequenced 2,335 cases and 789 controls in 10 candidate loci (57 genes). To increase power, we augmented our control set with ancestry-matched exome-sequenced controls. An analysis of coding variation in 2,268 AMD cases and 2,268 ancestry-matched controls identified 2 large-effect rare variants: previously described p.Arg1210Cys encoded in the CFH gene (case frequency (f case) = 0.51%; control frequency (f control) = 0.02%; odds ratio (OR) = 23.11) and newly identified p.Lys155Gln encoded in the C3 gene (f case = 1.06%; f control = 0.39%; OR = 2.68). The variants suggest decreased inhibition of C3 by complement factor H, resulting in increased activation of the alternative complement pathway, as a key component of disease biology.
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| doi.org/10.1038/ng.2758, hdl.handle.net/1765/54115 | |
| Nature Genetics | |
| Organisation | Department of Ophthalmology |
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Zhan, X., Larson, D., Wang, C., Koboldt, D., Sergeev, Y., Fulton, R., … Abecasis, G. (2013). Identification of a rare coding variant in complement 3 associated with age-related macular degeneration. Nature Genetics, 45(11), 1375–1381. doi:10.1038/ng.2758 |
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