title: Association of Smoking and CFH and ARMS2 Risk Variants With Younger Age at Onset of Neovascular Age-Related Macular Degeneration.
abstract: OBJECTIVE
  The age at which the first signs of age-related macular degeneration (AMD) manifest is variable. Better insight into factors that influence disease onset has direct implications for preventive measures and patient counseling.
  
  
  OBJECTIVE
  To identify risk factors for an earlier age at onset of neovascular AMD.
  
  
  METHODS
  Retrospective cohort study, including patient data from the European Genetic Database collected between April 2006 and July 2010. All patients had at least 1 documented visit to the outpatient AMD clinic of the Radboud University Medical Center, Nijmegen, the Netherlands, a tertiary referral center for retinal disorders. In total, 275 patients with a known age at onset of neovascular AMD and a genetic risk analysis were included.
  
  
  METHODS
  Effects of several genetic, sociodemographic, behavioral, and ocular factors on the age at onset of neovascular AMD. The mean differences in the age at onset were determined using general linear models with the age at onset as the dependent variable.
  
  
  RESULTS
  Past smokers and current smokers developed neovascular AMD on average 4.9 (95% CI, 3.0-6.8) and 7.7 (95% CI, 5.3-10.0) years earlier, respectively, than never smokers (P < .001 for both). Compared with the reference group, the age at onset was 5.2 (95% CI, 2.8-7.7) years earlier for homozygous carriers of the A69S risk allele in the age-related maculopathy susceptibility 2 (ARMS2) gene (P < .001). Homozygous carriers of the Y402H risk variant in the complement factor H (CFH) gene developed neovascular AMD 2.8 (95% CI, 0.5-5.0) years earlier (P = .02). Patients carrying 4 risk alleles in CFH and ARMS2 developed neovascular AMD 12.2 (95% CI, 6.2-18.3) years earlier than patients with zero risk alleles (P < .001).
  
  
  CONCLUSIONS
  Genetic and environmental risk factors influence the age at onset of neovascular AMD. Individuals at risk could be identified at an early age if and when preventive or therapeutic options become available. Insight into individual risk profiles might influence patients' consideration of interventions to increase their chance of avoiding vision loss from AMD.
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Yara T E
authors.initials: YT
authors.lastname: Lechanteur
authors.affiliation: University Eye Clinic Maastricht, Maastricht, the Netherlands.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: van de Camp
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Dzenita
authors.initials: D
authors.lastname: Smailhodzic
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Johannes P H
authors.initials: JP
authors.lastname: van de Ven
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands4Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Gabriëlle H S
authors.initials: GH
authors.lastname: Buitendijk
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands4Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.affiliation: Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Joannes M M
authors.initials: JM
authors.lastname: Groenewoud
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands6Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: B Jeroen
authors.initials: BJ
authors.lastname: Klevering
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D059647:Gene-Environment Interaction; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*; D011795:Surveys and Questionnaires; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; D011506:Proteins; D017242:Complement Factor H