Quite often the resulting list of phenotypes associated with a specific gene may include the major disease phenotype followed by specific sub-phenotypes of the disease that contribute distinct aspects to the overall clinical disease phenotype. For example, IL13 has been associated with asthma at least 11 times as well as to the asthma sub-phenotype immediate hypersensitivity 4 times. Similarly, the gene CFH has been associated with macular degeneration at least 19 times, as well as to the endophenotype of macular degeneration, choroidal neovascularization 3 times. Although replication in genetic association studies has been widely debated [22] , consistent replication by independent groups, although sometimes with both modest risk and significance values [23] , suggests a fundamental measure of scientific validity. This is true for both candidate gene as well as GWAS studies.