In individuals with alcohol dependence, there is a complex interplay between genetic background, environmental factors, and history of alcohol exposure3. Alcohol crosses the blood brain barrier and triggers changes in the central nervous system4, including transcriptional changes in many different regions of the brain5–9. The transcriptional effects of long-term alcohol consumption are associated with pathways involved in the neuro-immune system, neurotoxicity, and changes in neuroplasticity6,7,9. Transcriptomes from complex tissues, such as human brain, may be organized into networks of co-expressed genes that better reflect the biological functions and organization of the tissue7–14. Application of bioinformatics techniques, such as weighted gene co-expression network analysis (WGCNA)15, has uncovered networks associated with alcohol dependence8,9. However, past studies were performed on small numbers of AD cases, thus limiting the statistical power to detect small changes in alcohol-induced gene expression. In this study, we utilized massively parallel sequencing of RNA transcripts from postmortem human prefrontal cortex (PFC) of 65 alcoholics and 73 controls of European descent to explore transcriptional networks and genetic variation and identified groups of coexpressed genes associated with alcohol dependence. Our analysis provides systems-level evidence of genetic networks within the PFC that contribute to the pathophysiology of alcohol drinking behavior in humans.
