Genetics of pigment changes and geographic atrophy

PURPOSE. Studies of age-related macular degeneration (AMD) often involve persons with both choroidal neovascularization and geographic atrophy (GA), but few genome-wide scans (GWSs) have discriminated between these two outcomes. METHODS. To comprehend the role of pigmentary abnormalities (PA) and GA in AMD, the authors analyzed the data from a previous GWS on AMD (FARMS [Family Age-Related Maculopathy Study]sample of 34 extended families) looking only at PA. Presented are new GWS data from the full Beaver Dam Eye Study (BDES) family cohort, including longitudinal data at baseline and 5- and 10-year follow-up. A linkage analysis for PA/GA was performed on both samples for 338 markers covering all autosomes. Another linkage analysis using the rate of change along the PA/GA scale was performed with the BDES sample. RESULTS. Analysis of the FARMS sample provided evidence for linkage with P < 0.01 in the 1q25, 5p13, 6q21-23, and 11q14 regions. The most significant peak was found on chromosome 1, near complement factor H (CFH), with P = 6.20 × 10^-4. Analysis using the rate of change in BDES replicated the peaks in 5p13 and 6q21-23, suggesting that these loci may contribute to the rate of progression of PA/GA. Association analysis of CFH polymorphisms suggest that CFH may play a role in the development of pigmentary abnormalities and may modify the progression along the PA/GA scale. CONCLUSIONS. These findings suggest a complex, heterogeneous model for PA/GA.