title: Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages.
abstract: BACKGROUND
  Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factors and different AMD stages depending on unilateral and bilateral disease severity.
  
  
  METHODS
  In this case-control study, participants were assigned to nine AMD severity stages based on the characteristics of each eye. 18 single nucleotide polymorphisms (SNPs) were genotyped and attempted to correlate with AMD severity stages by uni- and multivariate logistic regression analyses and trend analyses. Area under the receiver operating characteristic curves (AUC) were calculated.
  
  
  RESULTS
  Of 3444 individuals 1673 were controls, 379 had early AMD, 333 had intermediate AMD and 989 showed late AMD stages. With increasing severity of disease and bilateralism more SNPs with significant associations were found. Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71). Trend analyses showed p<0.0001 for ARMS2 (rs10490924) and for CFH (rs1061170), respectively. AUC of risk models for various AMD severity stages was lowest for unilateral early AMD (AUC = 0.629) and showed higher values in more severely and bilaterally affected individuals being highest for late AMD with GA in one eye and neovascular AMD in the other eye (AUC = 0.957).
  
  
  CONCLUSIONS
  The association of known genetic risk factors with AMD became stronger with increasing disease severity, which also led to an increasing discriminative ability of AMD cases and controls. Genetic predisposition was also associated with the disease severity of the fellow-eye, highlighting the importance of both eyes in AMD patients.
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Schick
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Lebriz
authors.initials: L
authors.lastname: Altay
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Viehweger
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: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Felsch
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Fauser
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012372:ROC Curve
chemical_list: C514392:ARMS2 protein, human; D011506:Proteins