While there are several instances of important, influential markers that have been discovered in some common diseases, such as APOE in Alzheimer's, ARMS2 and CFH in age-related macular degeneration (AMD), and numerous alleles in the MHC region for autoimmune and inflammatory diseases, many genetic linkage results are the result of multiple infrequent alleles and most replicated markers from GWAS have modest effect sizes. This evidence concerns the gene APOE and age-related macular degeneration.