title: Extramacular drusen are highly associated with age-related macular degeneration, but not with CFH and ARMS2 genotypes.
abstract: BACKGROUND
  To evaluate the association of extramacular drusen (EMD) with age-related macular degeneration (AMD) and with complement factor H (CFH rs1061170) and age-related maculopathy susceptibility 2 (ARMS2 rs10490924) polymorphisms in individuals with and without AMD.
  
  
  METHODS
  In this case-control study, AMD staging was performed in 622 individuals. EMD were defined as ≥10 drusen (including ≥1 intermediate drusen) outside the Early Treatment of Diabetic Retinopathy Study Grid within field 2. Genotype associations for CFH and ARMS2 variants were assessed using logistic regression analysis.
  
  
  RESULTS
  EMD (n=213) showed a strong association with AMD (OR=3.85; p=1.66×10(-13)). AMD (n=316) was strongly associated with CFH (p=1.78×10(-7)) and ARMS2 genotypes (p=1.67×10(-8)). After adjustment for AMD, age and gender, EMD were neither associated with CFH (p=0.11) nor with ARMS2 (p=0.45) genotypes. In individuals without AMD, the groups with and without EMD showed no differences regarding both genetic variants.
  
  
  CONCLUSIONS
  The strong association between drusen within and outside of the macula suggests a common pathogenesis. However, EMD were not AMD-independently associated with CFH or ARMS2 genotypes. Our results indicate that patients without AMD but with EMD can serve as controls in studies evaluating AMD risk factors. Further studies are required to elucidate the aetiology and clinical relevance of EMD.
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany Department of Ophthalmology, Cologne Image Reading Center, University Hospital of Cologne, Cologne, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Ersoy
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany Department of Ophthalmology, Cologne Image Reading Center, University Hospital of Cologne, Cologne, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schick
authors.affiliation: Department of Ophthalmology, Cologne Image Reading Center, University Hospital of Cologne, Cologne, Germany.
authors.forename: D
authors.initials: D
authors.lastname: de Graft
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Felsch
authors.affiliation: Department of Ophthalmology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: C B
authors.initials: CB
authors.lastname: Hoyng
authors.affiliation: Department of Ophthalmology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: A I
authors.initials: AI
authors.lastname: den Hollander
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kirchhof
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Fauser
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany Department of Ophthalmology, Cologne Image Reading Center, University Hospital of Cologne, Cologne, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Liakopoulos
mesh_terms: D000368:Aged; D017242:Complement Factor H / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000000981:diagnostic imaging*; D015593:Retinal Drusen / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D041623:Tomography, Optical Coherence
chemical_list: C514392:ARMS2 protein, human; D011506:Proteins; D017242:Complement Factor H; D004247:DNA
keywords: Genetics; Imaging; Macula