A related impediment to AD gene finding is the phenotypic complexity of the disorder, especially when using a diagnosis-based phenotype. An alternative to DSM diagnosis-based phenotypes are intermediate phenotypes, which have been proposed to be more closely related to the specific genetic mechanisms and biological pathways underlying disease risk, thus having the potential to enhance gene identification (Goldman and Ducci, 2007). Several GWAS have already been performed for AD intermediate phenotypes such as alcohol consumption, briefly mentioned above (Baik et al., 2011; Frank et al., 2012; Gelernter et al., 2014a; Kapoor et al., 2013; Park et al., 2013; Quillen et al., 2014; Schumann et al., 2011; Takeuchi et al., 2011), and are likely to become increasingly popular in light of initiatives such as the NIMH Research Domain Criteria (RDoC) Project (Insel et al., 2010).
