The association of variants in complement factors H and B with age-related macular degeneration has led to more intense genetic and functional analysis of the complement pathway. We identify a nonsynonymous coding change in complement factor 3 that is strongly associated with risk of age-related macular degeneration in a large case-control sample.

1. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
2. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
3. Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts-New England Medical Center, 750 Washington St. #450, Boston, Massachusetts 02111, USA.
4. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London SE5 8AP, UK.
5. Harvard Medical School, Boston, Massachusetts 02115, USA.

Correspondence to: Johanna M Seddon³ e-mail: jseddon@tufts-nemc.org

Correspondence to: Mark J Daly^1,2,5 e-mail: mjdaly@chgr.mgh.harvard.edu

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