Evidence map›Paper›PMID 40742457›Full record

SynthesisCellular and molecular neurobiology2025

A GWAS Meta-meta-analysis and In-depth Silico Pharmacogenomic Investigations in Identification of APOE and Other Genes Associated with Pain, Anti-inflammatory, and Immunomodulating Agents in Opioid Use Disorder (OUD) Derived from 14.91 M Subjects.

Alireza Sharafshah, Majid Motovali-Bashi, Kenneth Blum, Kai-Uwe Lewandrowski, Mark S Gold, Parvaneh Keshavarz, Panayotis K Thanos

Abstract readMeta-Analysis
In one paragraph

Synthesis in Cellular and molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

7 authors.

Alireza SharafshahDivision of Genetics, Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.ORCID http://orcid.org/0000-0001-8048-9587
Majid Motovali-BashiDivision of Genetics, Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran. mbashi@sci.ui.ac.ir.ORCID http://orcid.org/0000-0003-4380-0166
Kenneth BlumDivision of Addiction Research & Education, Center for Sports, Exercise & Mental Health, Western University, Health Sciences, Pomona, CA, USA. drd2gene@gmail.com.ORCID http://orcid.org/0000-0001-6727-803X
Kai-Uwe LewandrowskiDivision of Personalized Pain Medicine & Education, Center for Advanced Spine Care of Southern Arizona, Tucson, AZ, USA.ORCID http://orcid.org/0000-0001-7842-2914
Mark S GoldDepartment of Psychiatry, Washington University, St. Louis, MO, USA. mgold9876@wustl.edu.ORCID http://orcid.org/0000-0001-7138-8047
Parvaneh KeshavarzCellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.ORCID http://orcid.org/0000-0002-1093-6051
Panayotis K ThanosBehavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, Clinical Research Institute on Addictions, State University of New York at Buffalo, Buffalo, NY, USA. thanos@buffalo.edu.ORCID http://orcid.org/0000-0002-5663-3478

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study aimed to integrate genome-wide association studies (GWAS) with pharmacogenomics data to develop personalized pain and inflammatory therapeutics. Despite recent developments in the clinical utilities of pharmacogenomics, it needs more investigations for uncovering the complicated mechanisms of drugs from a genetic standpoint. The research addresses the increasing misuse of opioids during recovery, emphasizing personalized interventions for opioid use disorder (OUD). Key pain-related pathways were analyzed to uncover their interactions. Five GWAS traits, including pain, inflammatory biomarkers, immune system abnormalities, and opioid-related traits, were examined. Candidate genes extracted from GWAS datasets were refined through in silico analyses, including protein-protein interactions (PPIs), TF-miRNA coregulatory interactions, enrichment analysis (EA), and clustering enrichment analysis (CEA). A network of 50 highly connected genes was identified, with APOE emerging as a top candidate due to its role in cholesterol metabolism and opioid-induced lipid effects. Pharmacogenomics analysis highlighted significant gene annotations, including OPRM1, DRD2, APOE, GRIN2B, and GPR98, linking them to opioid dependence, neurological disorders, and lipid traits. Protein interaction analyses further validated these connections, with implications for epigenetic repair. Our findings reveal a strong association between APOE, opioid use, and Alzheimer's disease, suggesting potential for novel recovery strategies. Combining HDL-boosting drugs with pro-dopaminergic regulators like KB220 may help prevent relapse. This study underscores the importance of integrating genetic and pharmacogenomic data to advance personalized therapies.

Indexed as

Anti-Inflammatory AgentsApolipoproteins EComputer SimulationGenome-Wide Association StudyImmunologic FactorsOpioid-Related DisordersPainPharmacogeneticsHumansAnti-Inflammatory AgentsApoE protein, humanApolipoproteins EImmunologic FactorsAPOEGWASLipidsMeta-meta-analysisOpioidsPain

Identifiers

PMID40742457
PMCPMC12314298

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.