Expanded genome scan in extended families with age-related macular degeneration

PURPOSE. To investigate further the genetic contribution to age-related macular degeneration (AMD), increasing the power of a previous analysis and reproducing the original findings. METHODS. A large cohort of families with this condition was assembled, and an expanded genome scan was performed with 556 microsatellite markers. In 2003, the results were reported of a genome-wide linkage analysis of 70 of these pedigrees. Members of 51 new families have now been ascertained and many of the original pedigrees expanded. Parametric and non-parametric linkage analyses were performed with a denser map of markers. In addition, analyses were performed with the sample stratified by age at ascertainment and by two major advanced phenotypes for the disease: neovascular AMD ( choroidal neovascularization) and geographic atrophy. RESULTS. The results corroborate the macular degeneration susceptibility loci consistently reported by the authors and others in genome-wide scans. New loci were identified, including the finding of a two-point HLOD of 3.70 at 6q25.2. CONCLUSIONS. The results suggest that the use of families enriched in predisposition to AMD has legitimacy. Genetic analyses of a genome-wide scan performed on our large cohort of families add further confirmatory evidence that susceptibility loci lie on 1q, 3p, 9q, and 10q. Furthermore, new loci have been identified, including a locus on 6q.