title: Age-related macular degeneration phenotypes associated with mutually exclusive homozygous risk variants in CFH and HTRA1 genes.
abstract: OBJECTIVE
  To determine age-related macular degeneration (AMD) phenotypes associated with mutually exclusive homozygotic risk variants in rs1061170 (CFH) and rs11200638 (HTRA1).
  
  
  METHODS
  Nested case-control study of 2,982 eyes (2,129 control, 809 drusen ≥125 μm, 44 advanced AMD) homozygous for CFH [TT or CC] and HTRA1 [GG or AA] were analyzed using logistic regression and generalized estimating equations specifically regards to homozygous risk variants in one but homozygous no-risk in the other gene.
  
  
  RESULTS
  In early AMD, [CFH HTRA1] and [CFH HTRA1] were associated with central drusen (odds ratio [95% confidence interval] = 4.13 [2.97-5.73] and 3.65 [1.88-7.09], respectively). However, only [CFH HTRA1] was associated with central drusen occupying ≥50% area (13.9 [2.97-64.7]). In advanced AMD, [CFH HTRA1] was associated with geographic atrophy (4.04 [1.57-10.4]), whereas [CFH HTRA1] was associated with neovascular AMD (36.5 [8.3-160.9]). In doubly homozygous risk groups [CFH HTRA1], odds ratios were multiplicative.
  
  
  CONCLUSIONS
  Central but not peripheral drusen location was strongly associated with both [CFH HTRA1] and [CFH HTRA1]. Only [CFH HTRA1] was significantly associated with increased central drusen area.
authors: *Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia; †Department of Psychological Science and Statistics, Swinburne University of Technology, Hawthorn, Victoria, Australia; and ‡Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore.
authors: Elaine W
authors: EW
authors: Chong
authors: Fakir M
authors: FM
authors: Amirul Islam
authors: Liubov D
authors: LD
authors: Robman
authors: Khin Zaw
authors: KZ
authors: Aung
authors: Andrea J
authors: AJ
authors: Richardson
authors: Paul N
authors: PN
authors: Baird
authors: Robyn H
authors: RH
authors: Guymer
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006720:Homozygote; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015593:Retinal Drusen / Q000235:genetics*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases