title: Genome-wide analysis of copy number variants in age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) is a complex genetic disease, with many loci demonstrating appreciable attributable disease risk. Despite significant progress toward understanding the genetic and environmental etiology of AMD, identification of additional risk factors is necessary to fully appreciate and treat AMD pathology. In this study, we investigated copy number variants (CNVs) as potential AMD risk variants in a cohort of 400 AMD patients and 500 AMD-free controls ascertained at the University of Iowa. We used three publicly available copy number programs to analyze signal intensity data from Affymetrix GeneChip SNP Microarrays. CNVs were ranked based on prevalence in the disease cohort and absence from the control group; high interest CNVs were subsequently confirmed by qPCR. While we did not observe a single-locus "risk CNV" that could account for a major fraction of AMD, we identified several rare and overlapping CNVs containing or flanking compelling candidate genes such as NPHP1 and EFEMP1. These and other candidate genes highlighted by this study deserve further scrutiny as sources of genetic risk for AMD.
authors.affiliation: Interdisciplinary Genetics Program, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Kacie J
authors.initials: KJ
authors.lastname: Meyer
authors.forename: Lea K
authors.initials: LK
authors.lastname: Davis
authors.forename: Emily I
authors.initials: EI
authors.lastname: Schindler
authors.forename: John S
authors.initials: JS
authors.lastname: Beck
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Rudd
authors.forename: A Jason
authors.initials: AJ
authors.lastname: Grundstad
authors.forename: Todd E
authors.initials: TE
authors.lastname: Scheetz
authors.forename: Terry A
authors.initials: TA
authors.lastname: Braun
authors.forename: John H
authors.initials: JH
authors.lastname: Fingert
authors.forename: Wallace L
authors.initials: WL
authors.lastname: Alward
authors.forename: Young H
authors.initials: YH
authors.lastname: Kwon
authors.forename: James C
authors.initials: JC
authors.lastname: Folk
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Russell
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Wassink
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D020256:Choroidal Neovascularization / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D003598:Cytoskeletal Proteins; D056915:DNA Copy Number Variations / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007484:Iowa / Q000453:epidemiology; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; C108725:NPHP1 protein, human