One gene set survived the multiple test correction threshold (regulation of intracellular steroid hormone reception signaling pathway), and scrutiny of the genes in that category (obtained from MSigDB) revealed a potentially interesting avenue for further inquiry: they include core clock genes involved in circadian rhythms and/or photoperiodism, which were among the top 10 most strongly implicated gene sets (Supplemental Table 2). Genes included in all three sets are CLOCK, CRY1, CRY2, and PER1; other clock genes are common to two of the three sets. CLOCK and PER1 have been associated with alcohol use disorders (Partonen, 2015), and there is evidence that clock genes may have a regulatory role in reward circuitry (Parekh et al., 2015). Furthermore, mice with various perturbations in clock genes exhibit aberrant alcohol-related phenotypes (Dong et al., 2011; Gamsby et al., 2013; Perreau-Lenz et al., 2009; Spanagel et al., 2005; Wang et al., 2012).
