We also found evidence for enrichment (q-values⩽0.05) across multiple canonical pathways and gene ontologies including cytokine activity, Jak-STAT signaling pathway, toll-like receptor signaling pathway, antigen processing and presentation, cytokine receptor binding and natural killer cell-mediated cytotoxicity. Although the immediate biological relevance of these categories to AAB is not clear, these enrichment findings include many immune-related pathways and may be best interpreted in light of the associations among AAB and alcohol, cannabis, cocaine and opioid dependence criterion counts in the sample. Immune and inflammatory pathways have been hypothesized to be associated with psychiatric disorders across the internalizing and externalizing spectra.46 For example, it is known that alcohol alters cytokine activity,47 induces changes in neuroimmune signaling in the brain48 and that alcohol dependence is associated with low-grade systemic inflammation.49 Likewise, the monocytes of individuals who are cocaine dependent show decreased expression of tumor necrosis factor-α and interleukin-6 proinflammatory cytokines in response to a bacterial ligand relative to controls.50 Four of the top genes (based on P-values) to emerge in our analysis are genes for type I interferon (IFNA7, IFNA10, IFNA16 and IFNA17),
