Trait-module correlation analysis for the thistle2 module showed a significant negative correlation with alcohol dependence (−0.28, P = 9.0 × 10−4), alcohol consumption (−0.22, P = 9.0 × 10−3), and AUDIT score (−0.25, P = 3.0 × 10−3), while the brown4 module showed a positive correlation (0.18, P = 4.0 × 10−2) with alcohol dependence (Fig. 2; Table 2). The salmon4 module was associated with the total number of drinking years (−0.24, P = 4.0 × 10−3), independent of the age of the subjects. Genes in the thistle2 module were significantly downregulated in the PFC from alcoholics. Many genes in the thistle2 module mapped to networks involved in opioid signaling and nicotine response, highlighting the importance of this module in addiction-related traits. Pathway analysis showed that all genes that overlapped with genes involved in calcium signaling were significantly downregulated (Fig. 3a). Acute ethanol exposure has been shown to inhibit Ca2+ currents induced by PKC-dependent phosphorylation of mGluR5 in neurons42. Early studies in PC12 cell cultures also showed that ethanol has a significant inhibitory effect on the influx of Ca2+ through
