TY - JOUR
T1 - Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex
AU - Traumatic Stress Brain Research Group
AU - Rompala, Gregory
AU - Nagamatsu, Sheila T.
AU - Martínez-Magaña, José Jaime
AU - Nuñez-Ríos, Diana L.
AU - Wang, Jiawei
AU - Girgenti, Matthew J.
AU - Krystal, John H.
AU - Gelernter, Joel
AU - Alvarez, Victor E.
AU - Benedek, David
AU - Che, Alicia
AU - Cruz, Dianne A.
AU - Davis, David A.
AU - Girgenti, Matthew J.
AU - Hoffman, Ellen
AU - Holtzheimer, Paul E.
AU - Huber, Bertrand R.
AU - Kaye, Alfred
AU - Krystal, John H.
AU - Labadorf, Adam T.
AU - Keane, Terence M.
AU - Logue, Mark W.
AU - McKee, Ann
AU - Marx, Brian
AU - Miller, Mark W.
AU - Noller, Crystal
AU - Montalvo-Ortiz, Janitza
AU - Scott, William K.
AU - Schnurr, Paula
AU - Stein, Thor
AU - Ursano, Robert
AU - Williamson, Douglas E.
AU - Wolf, Erika J.
AU - Young, Keith A.
AU - Hurd, Yasmin L.
AU - Montalvo-Ortiz, Janitza L.
N1 - Publisher Copyright:
© 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85165960564&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-40285-y
DO - 10.1038/s41467-023-40285-y
M3 - Article
C2 - 37507366
AN - SCOPUS:85165960564
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4544
ER -