Include the weighted sum method described by Madsen and Browning (2009)^{ 1 }; a variable -threshold approach (Price et al . 2010)^{ 2 }with or without weights such as PolyPhen-2 scores; models taking the direction of the variant's effect into account, similar to Han and Pan's data-adaptive sum model (2010)^{ 3 }; as well as combinations of these approaches that can be put into the framework described by Hoffmann, Marini, and Witte (2010)^{ 4 }.