Genome-wide analysis of copy number variants in age-related macular degeneration

• Published in: Human genetics 2011-01, Vol.129 (1), p.91-100
• Main Authors: Meyer, Kacie J, Davis, Lea K, Schindler, Emily I, Beck, John S, Rudd, Danielle S, Grundstad, A. Jason, Scheetz, Todd E, Braun, Terry A, Fingert, John H, Alward, Wallace L, Kwon, Young H, Folk, James C, Russell, Stephen R, Wassink, Thomas H, Stone, Edwin M, Sheffield, Val C
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Age; Aged; Aged, 80 and over; Analysis; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Choroidal Neovascularization - epidemiology; Choroidal Neovascularization - genetics; Classical genetics, quantitative genetics, hybrids; Cohort Studies; DNA Copy Number Variations - genetics; Extracellular Matrix Proteins - genetics; Eye diseases; Female; Fundamental and applied biological sciences. Psychology; Gene Function; Genes; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Genomes; Genomics; Health risk assessment; Human; Human Genetics; Humans; Iowa - epidemiology; Macular degeneration; Macular Degeneration - epidemiology; Macular Degeneration - genetics; Male; Medical sciences; Membrane Proteins - genetics; Metabolic Diseases; Molecular Medicine; Ophthalmology; Original Investigation; Patients; Physiological aspects; Polymorphism, Single Nucleotide; Prevalence; Retinopathies; Risk Factors
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-010-0904-6

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.