We also identified other genes that might be involved in increased alcohol consumption through a variety of biological mechanisms. For example, VPS4A at 16q23.1 has been implicated in dopamine regulation, reward anticipation, and hyperactivity in an fMRI study44. We also identified functional variants for SULT1A1 and SULT1A2 genes that encode for Sulfotransferase Family 1A enzymes catalyzing the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds45. In IPA disease enrichment analysis, we observed a nominally significant overlap between genes implicated in DPW with other neurological, behavioral and immune-related disorders (Supplementary Fig 16). The genes associated with DPW also showed significant enrichment for pathways related to TR/ RXR activation, Lipoate biosynthesis, Estrogen biosynthesis, and Sirtuin signaling (Supplementary Data 8). TRs (Thyroid hormone receptor) control the expression of target genes involved in diverse physiological processes and diseases, such as metabolic syndrome, obesity, and cancer, and, therefore, are considered as important targets for therapeutic drug development46. RXRs (Retinoic X Receptor) are known to potentially regulate the ethanol metabolizing enzymes after chronic alcohol consumption47. It has been reported that the human aldehyde dehydrogenase-2
