In consideration of the heterogeneous gene-gene relationships between the major risk variants of the CFH, ARMS2, and HTRA1 loci, several Authors have emphasized the consistent possibility of an independent multiplicative joint effect in AMD, also taking into account that each of them should be contextualized within gene-environment interactions and epigenetic aspects [22–25, 49, 139, 140]. This evidence concerns the gene HTRA1 and age-related macular degeneration.