These examples are specific to alcohol, but the idea of heterogeneous genetically-influenced pathways is likely to be broadly applicable to psychiatric/substance use disorders. Heterogeneity in symptoms, course, and etiology of disorders is recognized as a profound challenge in studying psychopathology (Dacquino et al., 2015, Geschwind & Flint, 2015, Hines et al., 2005, Lee et al., 2016, Milaneschi et al., 2016, Wium-Andersen et al., 2017). Although this challenge makes gene identification a particularly difficult undertaking, it is hypothesized to be overcome by “brute force” approaches with large sample sizes, as described above (e.g. Schizophrenia Working Group, 2014; Wood et al. 2014). These methods, however, point only to which genetic variants are important but not why, so post-gene identification it will be important to test identified variants in a more nuanced and specific way to understand through which of many possible pathways that gene influences the phenotype (Geschwind & Flint, 2015, Mackay et al., 2009). For example, one could test whether genetic markers identified as associated with alcohol dependence influence a person’s biological or subjective response to alcohol or whether they influence
