hMRS significantly outperformed MRS in predicting Opioid Use Disorder, explaining 33.5% of the variance compared to 12% for MRS.
null (n=153)
Hydroxymethylation risk scores (hMRS) outperform methylation risk scores (MRS) in predicting opioid use disorder using postmortem brain tissue, highlighting the importance of distinguishing between 5mC and 5hmC.
Effect estimate: null (95% CI null)
p-value: p=0.0001
Opioid use disorder (OUD) poses significant global health and socioeconomic burden. While epigenetic mechanisms, particularly DNA methylation (5mC), have been implicated in OUD, recent work from our group has revealed an important role of DNA hydroxymethylation (5hmC). Building on prior work, we aimed to construct epigenetic risk scores as tools to help predict OUD. Methylation and hydroxymethylation risk scores (MRS/hMRS) were calculated and evaluated for their predictive ability, variance explained, and functional significance. Our results revealed that hMRS outperforms MRS in predicting OUD, with a variance explained of 33.5%. The combined MRS and hMRS explained 34.5% of the variance in OUD. Functional analysis revealed enrichment for Wnt signaling and embryonic development. Gene interaction networks implicated genes involved in opioid signaling pathway and unveiled potential novel gene candidates. This study further supports the importance of distinguishing between 5mC and 5hmC to further understand the epigenetic landscape of OUD. The higher predictive accuracy of hMRS along with hMRS's functional pathways and networks provide valuable insights into the molecular underpinnings of OUD.
Heredia et al. (Fri,) conducted a null in Opioid Use Disorder (n=153). null vs. null was evaluated on Association of MRS and hMRS with OUD (null, 95% CI null, p=0.0001). hMRS significantly outperformed MRS in predicting Opioid Use Disorder, explaining 33.5% of the variance compared to 12% for MRS.