The phenome-wide genetic-correlation analyses identified correlations with numerous traits including tobacco smoking behaviors, socioeconomic status, physical activity, reproductive behaviors, fat mass, personality traits, and, to a lesser extent, certain psychiatric disorders. Similar findings have been reported previously, even with small numbers of markers or with ADH1B*rs1229984 taken individually (56). These genetic relationships of MaxAlc are consistent with the pervasive role of alcohol use and abuse on human morbidity and mortality (57). Gene-based analysis, besides supporting CRHR1 as noted above, supported other genes associated in SNP-based analysis such as XPO7 and FGF14, as well as, for example, KANSL1, which maps to the same inversion region as CRHR1, and PDE4B (Phosphodiesterase 4B), previously implicated in other neuropsychiatric disorders. Tissue and human cell-type expression enrichments were noted for cerebellar hemisphere and cerebellum; dopaminergic and GABAergic neurons in human midbrain; and delta cells in pancreas. The cerebellar enrichment is particularly relevant with respect to the known effects of alcohol on this brain region: ethanol is the most common injurious agent to Purkinje cells (58, 59). In this context, inter-individual variability in the genetic regulation
