Gene modules in the upper quartile of lifetime alcohol consumption constituted two main groups (Fig. 2), with only Group1 being enriched for signals from GWAS of alcohol dependence. The lack of genetic association within GMs belonging to Group2 may by and large suggest a non-genetic, yet biologically related to Group1, set of molecular components affecting the neurobiology of alcohol intake. Chronic alcohol consumption, genetic factors, and associated environmental influences may bring about coordinately regulated molecular adaptations supporting brain function in addictive processes. GM19, a Group2 module, consists of genes encoding CNS white-matter proteins (MOBP, OPALIN, UGT8, and ERMN). Abnormal white-matter expression in the PFC plays an essential role in brain morphology and behavioral responses to alcohol and other drugs of abuse 68-70. Alterations in myelin-related proteins are capable of distorting axon-glial interactions and clustering of ion channels responsible for neuronal conduction 71, a prominent biological feature of the gene modules identified with association to alcohol drinking behavior. Group2 also contains long non-coding RNAs (ncRNAs) such as NCRNA00092, NCRNA00174, and NCRNA00284. The function of these ncRNAs is currently unknown, but may
