There are some caveats to our analyses. One limitation is that those who drink heavily are more likely to smoke70. Thus, some differences might be attributed in part to smoking. Nevertheless, these findings remain a valid reflection of the disease’s underlying biology, which often includes smoking. Another limitation is that our results are primarily from males genetically closely related to the 1000 Genomes European samples, and therefore do not capture the transcriptional and epigenetic diversity across ancestry groups or sexes71. AUD is more likely to occur in men, and our cohort demographics reflect this; thus, we did not have adequate statistical power for sex-specific analysis. Differential analysis did show some genes whose expression was significantly associated with sex (e.g., in astrocytes, 186 sex associated genes were identified with FDR < 0.05; age, ethnic origin, and AUD status as covariates). There were many gene expression differences associated with age (e.g., in astrocytes, 1908 age-associated genes were identified with FDR < 0.05; age, ethnic origin, and AUD status as covariates). However, since the AUD and non-AUD groups were age-matched (AUD average age
