Evidence map›Paper›PMID 36745154›Full record

ArticleFrontiers in psychiatry2022

CpH methylome analysis in human cortical neurons identifies novel gene pathways and drug targets for opioid use disorder.

Sheila T Nagamatsu, Gregory Rompala, Yasmin L Hurd, Diana L Núñez-Rios, Janitza L Montalvo-Ortiz, Traumatic Stress Brain Research Group

Open access · goldAbstract read
In one paragraph

Article in Frontiers in psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Sheila T NagamatsuDivision of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States.
Gregory RompalaIcahn School of Medicine at Mount Sinai, New York, NY, United States.
Yasmin L HurdIcahn School of Medicine at Mount Sinai, New York, NY, United States.
Diana L Núñez-RiosDivision of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States.
Janitza L Montalvo-OrtizDivision of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States.
Traumatic Stress Brain Research Group
Icahn School of Medicine at Mount Sinai · USNational Center for Post Traumatic Stress Disorder · USYale University · US

Funding

Transcription Factors in Stimulant and Opioid ActionP01DA047233 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Li Shen · 2019 to 2026
$16.5M
Deciphering the single-nucleus genomic regulatory structure of opioid use disorder in the human brainDP1DA058737 · NIDA · YALE UNIVERSITY · PI Janitza Liz Montalvo-Ortiz · 2023 to 2026
$2.0M
Integrative Epigenomic Mapping of Co-Morbid OUD and PTSD SupplementR21DA050160 · NIDA · YALE UNIVERSITY · PI MONTALVO-ORTIZ, JANITZA LIZ · 2020 to 2021
$433k
CSRD VA IK2 CX002095NIDA NIH HHS DP1 DA058737NIDA NIH HHS P01 DA047233NIDA NIH HHS R21 DA050160
6 · The paper itself

Abstract

Introduction: DNA methylation (DNAm), an epigenetic mechanism, has been associated with opioid use disorder (OUD) in preclinical and human studies. However, most of the studies have focused on DNAm at CpG sites. DNAm at non-CpG sites (mCpHs, where H indicates A, T, or C) has been recently shown to have a role in gene regulation and to be highly abundant in neurons. However, its role in OUD is unknown. This work aims to evaluate mCpHs in the human postmortem orbital frontal cortex (OFC) in the context of OUD. Methods: A total of 38 Postmortem OFC samples were obtained from the VA Brain Bank (OUD = 12; Control = 26). mCpHs were assessed using reduced representation oxidative bisulfite sequencing in neuronal nuclei. Differential analysis was performed using the "methylkit" R package. Age, ancestry, postmortem interval, PTSD, and smoking status were included as covariates. Significant mCpHs were set at Results: A total of 2,352 differentially methylated genome-wide significant mCpHs were identified in OUD, mapping to 2,081 genes. GO analysis of genes with differential mCpH loci showed enrichment for nervous system development ( Conclusion: Our findings suggest a role of mCpHs for OUD in cortical neurons and reveal important biological pathways and drug targets associated with the disorder.

Indexed as

epigeneticmethylationnon-CpG siteopioidorbitofrontal cortexpostmortem human brain

Identifiers

PMID36745154
PMCPMC9892724
OpenAlexW4317739183

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.