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<p>Only recently have human postmortem brain studies of differential gene expression (DGE) associated with opioid overdose death (OOD) been published; sample sizes from these studies have been modest (<i>N</i> = 40–153). To increase statistical power to identify OOD-associated genes, we leveraged human prefrontal cortex RNA-seq data from four independent OOD studies and conducted a transcriptome-wide DGE meta-analysis (<i>N</i> = 272). Using a unified gene expression data processing and analysis framework across studies, we meta-analyzed 20, 098 genes and found 335 significant differentially expressed genes (DEGs) by OOD status (false discovery rate &lt; 0.05). Of these, 66 DEGs were among the list of 303 genes reported as OOD-associated in prior prefrontal cortex molecular studies (e.g., genes/gene families <i>OPRK1, NPAS4</i>, <i>DUSP, EGR</i>). The remaining 269 DEGs were not previously reported (e.g., <i>NR4A2, SYT1, HCRTR2, BDNF</i>). There was little evidence of genetic drivers for the observed differences in gene expression between opioid addiction cases and controls. Enrichment analyses for the DEGs across molecular pathway and biological process databases highlight an interconnected set of genes and pathways linked to orexin and tyrosine kinase receptors through MEK/ERK/MAPK signaling to affect neuronal plasticity.</p>

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Identifying novel gene dysregulation associated with opioid overdose death: a meta-analysis of differential gene expression in human prefrontal cortex

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月8日

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  • Javan K. Carter,
  • Bryan C. Quach,
  • Caryn Willis,
  • Melyssa S. Minto,
  • Dana B. Hancock,
  • Janitza Montalvo-Ortiz,
  • Olivia Corradin,
  • Ryan W. Logan,
  • Consuelo Walss-Bass,
  • Brion S. Maher,
  • Angela Moissl,
  • Graciela Delgado,
  • Marcus Kleber,
  • Rodrigo Grassi-Oliveira,
  • Jerome Foo,
  • Stephanie Witt,
  • Eva Friedel,
  • Pierre-Eric Lutz,
  • Susanne Edelmann,
  • Vanessa Nieratschker,
  • Seyma Katrinli,
  • Howard Edenberg,
  • David Sosnowski,
  • Chloe Chung Yi Wong,
  • Diego Quattrone,
  • Edoardo Spinazzola,
  • Giulia Trotta,
  • Luis Alameda,
  • Marta Di Forti,
  • Robin Murray,
  • Yasmin Hurd,
  • Falk Lohoff,
  • Shyamala Venkatesh,
  • Vijay Ramchandani,
  • Bhagyalakshmi,
  • Jayant Mahadevan,
  • Meera Purushottam,
  • Thiago Wendt Viola,
  • Fang Fang,
  • Julie White,
  • Stephanie Giamberardino,
  • Winfried März,
  • Shauna Clark,
  • Lea Zillich,
  • Emma Dempster,
  • Ian Gizer,
  • Jacqueline Otto,
  • Leen Magarbeh,
  • Gabriel R. Fries,
  • Arpana Agrawal,
  • Emma Johnson,
  • Diego Andrade-Brito,
  • Ke Xu,
  • Diana Núñez,
  • Joel Gelernter,
  • Jose Jaime Martinez Magana,
  • Sheila Tiemi Nagamatsu,
  • Eric Otto Johnson

摘要

Only recently have human postmortem brain studies of differential gene expression (DGE) associated with opioid overdose death (OOD) been published; sample sizes from these studies have been modest (N = 40–153). To increase statistical power to identify OOD-associated genes, we leveraged human prefrontal cortex RNA-seq data from four independent OOD studies and conducted a transcriptome-wide DGE meta-analysis (N = 272). Using a unified gene expression data processing and analysis framework across studies, we meta-analyzed 20, 098 genes and found 335 significant differentially expressed genes (DEGs) by OOD status (false discovery rate < 0.05). Of these, 66 DEGs were among the list of 303 genes reported as OOD-associated in prior prefrontal cortex molecular studies (e.g., genes/gene families OPRK1, NPAS4, DUSP, EGR). The remaining 269 DEGs were not previously reported (e.g., NR4A2, SYT1, HCRTR2, BDNF). There was little evidence of genetic drivers for the observed differences in gene expression between opioid addiction cases and controls. Enrichment analyses for the DEGs across molecular pathway and biological process databases highlight an interconnected set of genes and pathways linked to orexin and tyrosine kinase receptors through MEK/ERK/MAPK signaling to affect neuronal plasticity.