The endophenotype concept is similar to, but distinct from, related concepts such as biomarkers and intermediate phenotypes [17]. Biomarkers refer to measurable indicators of a disease state. As noted by Lenzenweger [17], biomarkers are associated with the disease, but do not necessarily reflect a genetically influenced pathway. For example, in a biomedical context the ratio of aspartate aminotransferase to alanine aminotransferase can be used as a biomarker of alcoholic liver disease. In this case, the biomarker is associated with the disease, but does not reflect a genetically influenced enduring vulnerability to the disease. According to Rasetti and Weinberger, an intermediate phenotype is “a heritable trait that is located in the path of pathogenesis from genetic predisposition to psychopathology” [18]. This concept has been critiqued on account of its ambiguity with respect to where “intermediate” phenotypes lie along the pathway from genes → disorder, which has implications for level of analysis [17]. Thus, although the endophenotype, biomarker, and intermediate phenotype concepts share overlapping goals of clarifying heterogeneity, the terms are not interchangeable. For an extended discussion of these definitional issues, we refer interested readers to Lenzenweger [17].
