In a recent EWAS of AUD in postmortem brain tissue, we identified differentially methylated CpG-sites and regions in the ventral and dorsal striatum [15]. Previous studies have shown the utility of integrating epigenetic and transcriptomic data in postmortem brain tissue of SUDs using weighted correlation network analysis (WGCNA) [16]. WGCNA clusters genes or CpG-sites into co-expressed or co-methylated modules based on correlation matrices. By relating modules to each other, WGCNA can be used for data integration, providing more insights than descriptive overlap. For example, whereas a descriptive comparison of histone H3 lysine 4 trimethylation (H3K4me3) and mRNA expression in individuals with AUD and cocaine use disorder revealed no consistent overlap between H3K4me3 trimethylation and gene expression [17], a network analysis identified overlapping modules pointing towards co-expressed genes associated with H3K4me3 trimethylation [6]. Modules associated with AUD were enriched for CNS functions, such as synaptic transmission and regulation of neurogenesis [6]. WGCNA has also been used for integrating epigenetic and transcriptomic data and investigating their association with opioid use disorder (OUD) in postmortem human brain, identifying immune-related transcriptional regulation to be enriched in co-expressed and co-methylated modules [18].
