Abstract
Background/Aims Age-related macular degeneration (AMD) is the most common cause of vision loss in individuals over the age of 50 in the United States. Genetic factors explain a large portion of the risk of developing AMD, and genetic variants at the CFH, HTRA1/ARMS2, C2/CFB, and C3 gene loci have previously been associated with the disease.
Methods We conducted a genome-wide association study (GWAS) of AMD in the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. The GERA cohort includes 110,266 subjects with extensive electronic medical record information on eye examinations, diagnoses and treatment of vision disorders, and dense genome-wide genotype information on more than 675,000 genetic markers generated using Affymetrix Axiom arrays. The cohort is ethnically diverse, with 7.5% Asian, 7% Latino, 3.5% African American, and 81% non-Hispanic white subjects. We identified a total of 2,147 AMD cases (46 Asian, 125 Latino, 11 African American, and 1,965 non-Hispanic whites) and 37,521 controls (2,013 Asian, 3,201 Latino, 1,168 African American, and 31,139 non-Hispanic whites) for analysis. Analyses were conducted separately for each race/ethnicity group.
Results In the largest group, non-Hispanic whites, we identified highly significant associations with variants in the CFH and HTRA1/ARMS2 gene regions, and genome-wide significant associations in the C2/CFB and C3 gene regions.
Conclusions These results confirm those of previous studies and demonstrate the power of the GERA cohort for combining information from electronic medical records with extensive genotype data. This approach can be applied to additional vision disorder phenotypes, including response to treatment and disease progression.
