Profiling Neuronal Methylome and Hydroxymethylome of Opioid Use Disorder in the Human Orbitofrontal Cortex

Opioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests epigenetic disturbances in OUD, this is mostly limited to DNA methylation (5mC). DNA hydroxymethylation (5hmC) has been widely understudied. We conducted a multi-omics profiling of OUD in a male cohort, integrating neuronal-specific 5mC and 5hmC as well as gene expression profiles from human postmortem orbitofrontal cortex (OUD=12; non-OUD=26). Single locus methylomic analysis and co-methylation analysis showed a higher number of OUD-associated genes and gene networks for 5hmC compared to 5mC; these were enriched for GPCR, Wnt, neurogenesis, and opioid signaling. 5hmC marks also showed a higher correlation with gene expression patterns and enriched for GWAS of psychiatric traits. Drug interaction analysis revealed interactions with opioid-related drugs, some used as OUD treatments. Our multi-omics findings suggest an important role of 5hmC and reveal loci epigenetically dysregulated in OFC neurons of individuals with OUD. Postmortem orbitofrontal cortex tissue were obtained from the National Post-Traumatic Stress Disorder (PTSD) Brain Bank (NPBB), a brain tissue repository at the U.S. Department of Veterans Affairs (VA). 38 samples were selected, in which 12 individuals were diagnosed with opioid use disorder (OUD+) and 26 without opioid use disorder (OUD-). Traumatic Stress Brain Research Group ---------------------- Authors state: The original data is a RRoxBS. However, I only have the beta values table generated using the read counts for each site. I don't have the raw data to submit.