title: Genetic and environmental risk factors for age-related macular degeneration in persons 90 years and older.
abstract: OBJECTIVE
  We studied associations of genetic polymorphisms in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) in nonagenarians with age-related macular degeneration (AMD).
  
  
  METHODS
  This case-control study comprised 2737 persons (1204 controls, 1433 AMD cases), including 166 nonagenarians (52 controls, 114 AMD cases). Single nucleotide polymorphisms (SNPs) in the genes ARMS2 and CFH were determined. Risk scores were computed by multiple logistic regression analysis, including genetic and environmental risk factors (smoking, hypertension, body mass index, diabetes) for different age groups (<70, 70-79, 80-89, ≥ 90 years [nonagenarians]).
  
  
  RESULTS
  In nonagenarians, ARMS2 showed the weakest associations with AMD (odds ratio [OR] = 1.52, P = 0.127) compared to the other groups (OR, 70 years = 2.23, P = 1.03 × 10(-13); OR, 70-79 years = 2.70, P = 1.00 × 10(-13); OR, 80-89 years = 3.11, P = 6.56 × 10(-8)). For CFH, ORs for AMD increased with age (<70 years OR = 1.96, P = 1.80 × 10(-11); 70-79 years OR = 1.89, P = 4.48 × 10(-13); 80-89 years OR = 2.71, P = 1.28 × 10(-7)), but decreased again in the nonagenarians (OR = 2.21, P = 0.005). Compared to the group <70 years, reduced minor allele frequencies (MAFs) for AMD patients were observed in the nonagenarians (CFH 0.54 vs. 0.43, P = 0.009; ARMS2 0.44 vs. 0.29, P = 2.97 × 10(-5)), while the MAFs in controls were not significantly different. The genetic risk score revealed the lowest discriminative power in the nonagenarians with an area-under-curve (AUC) of 0.658 for receiver-operating characteristics (AUC 80-89 years = 0.768, 70-79 years = 0.704, <70 years = 0.682), while no significant difference was seen for the environmental risk score (AUC < 70 years = 0.579, 70-79 years = 0.567, 80-89 years = 0.600, >90 years = 0.608).
  
  
  CONCLUSIONS
  Risk alleles in CFH and ARMS2 have a significantly smaller effect on AMD development in nonagenarians, while environmental factors retain a similar effect.
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Lebriz
authors.initials: L
authors.lastname: Ersoy
authors.forename: Tina
authors.initials: T
authors.lastname: Ristau
authors.forename: Moritz
authors.initials: M
authors.lastname: Hahn
authors.forename: Marcus
authors.initials: M
authors.lastname: Karlstetter
authors.forename: Thomas
authors.initials: T
authors.lastname: Langmann
authors.forename: Katharina
authors.initials: K
authors.lastname: Dröge
authors.forename: Albert
authors.initials: A
authors.lastname: Caramoy
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Sascha
authors.initials: S
authors.lastname: Fauser
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D015995:Prevalence; D011506:Proteins / Q000235:genetics; D012307:Risk Factors
chemical_list: C514392:ARMS2 protein, human; D011506:Proteins; D004247:DNA
keywords: age; age-related macular degeneration; genetics