Identification of a rare coding variant in complement 3 associated with age-related macular degeneration.
Nat Genet
; 45(11): 1375-9, 2013 Nov.
Article
in En
| MEDLINE
| ID: mdl-24036949
ABSTRACT
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 (fcase) = 0.51%; control frequency (fcontrol) = 0.02%; odds ratio (OR) = 23.11) and newly identified p.Lys155Gln encoded in the C3 gene (fcase = 1.06%; fcontrol = 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Complement C3
/
Complement Pathway, Alternative
/
Macular Degeneration
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2013
Document type:
Article