title: Differences in the Genetic Susceptibility to Age-Related Macular Degeneration Clinical Subtypes.
abstract: OBJECTIVE
  We compared across age-related macular degeneration (AMD) subtypes the effect of AMD risk variants, their predictive power, and heritability.
  
  
  METHODS
  The prevalence of AMD was estimated among active non-Hispanic white Kaiser Permanente Northern California members who were at least 65 years of age as of June 2013. The genetic analysis included 5,170 overall AMD cases ascertained from electronic health records (EHR), including 1,239 choroidal neovascularization (CNV) cases and 1,060 nonexudative AMD cases without CNV, and 23,130 controls of non-Hispanic white ancestry from the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Imputation was based on the 1000 Genomes Project reference panel.
  
  
  RESULTS
  The narrow-sense heritability due to common autosomal single nucleotide polymorphisms (SNPs) was 0.37 for overall AMD, 0.19 for AMD unspecified, 0.20 for nonexudative AMD, and 0.60 for CNV. For the 19 previously reported AMD risk loci, the area under the receiver operating characteristic (ROC) curve was 0.675 for overall AMD, 0.640 for AMD unspecified, 0.678 for nonexudative AMD, and 0.766 for CNV. The individual effects on the risk of AMD for 18 of the 19 SNPs were in a consistent direction with those previously reported, including a protective effect of the APOE ε4 allele. Conversely, the risk of AMD was significantly increased in carriers of the ε2 allele.
  
  
  CONCLUSIONS
  These findings provide an independent confirmation of many of the previously identified AMD risk loci, and support a potentially greater role of genetic factors in the development of CNV. The replication of established associations validates the use of EHR in genetic studies of ophthalmologic traits.
authors.affiliation: Kaiser Permanente Division of Research Oakland, California, United States.
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.affiliation: Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States 3Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hoffmann
authors.affiliation: Department of Ophthalmology, Kaiser Permanente Northern California Redwood City Medical Center, Redwood City, California, United States.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Melles
authors.affiliation: Kaiser Permanente Division of Research Oakland, California, United States.
authors.forename: Lori C
authors.initials: LC
authors.lastname: Sakoda
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Kvale
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States.
authors.forename: Yambazi
authors.initials: Y
authors.lastname: Banda
authors.affiliation: Kaiser Permanente Division of Research Oakland, California, United States.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schaefer
authors.affiliation: Kaiser Permanente Division of Research Oakland, California, United States 3Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States 4Department of Ophthalmology, Kaiser Permanente North.
authors.forename: Neil
authors.initials: N
authors.lastname: Risch
authors.affiliation: Kaiser Permanente Division of Research Oakland, California, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Jorgenson
mesh_terms: D000368:Aged; D000483:Alleles; D002140:California / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors