{
  "id": 10531924,
  "title": "Identification of alcohol use disorder-associated and ethanol-responsive proteins and candidate biomarkers using human cortical organoids",
  "url": "https://urgent.news/2026/09/28/identification-of-alcohol-use-disorder-associated-and-ethanol",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-28T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.27.754852v1?rss=1"
  },
  "original_language": "en",
  "account": "Genome-wide association studies have pinpointed 100 regions linked to alcohol use disorder (AUD), yet the biological implications and underlying molecular pathways remain elusive. Proteins, acting as effectors of genes, offer direct insights into disease mechanisms. However, most alterations in proteins from human brains postmortem due to AUD are likely a result of a mix of genetic predisposition (AUD-associated), the effects of alcohol exposure (ethanol-responsive), other environmental and lifestyle factors, as well as sample preparation methods. In this study, researchers focused on the proteome of human microglia-containing cortical organoids cultivated from human induced pluripotent stem cells sourced from individuals with AUD (n=11) and without AUD (n=5). To bolster statistical significance, donors were chosen based on high or low genetic risk for AUD, as determined by polygenic scores. From the 8,952 proteins that met quality control standards, 1,038 were linked to AUD and 718 to ethanol exposure. AUD-associated proteins were found to be overrepresented in neuronal signaling, immune, mitochondrial, and extracellular matrix pathways, while ethanol-responsive proteins were more abundant in RNA processing, ribosome biogenesis, protein translation, vesicle trafficking, and membrane transport pathways. Twenty ethanol-responsive proteins were corroborated by a separate proteomic analysis of postmortem human prefrontal cortex samples. By leveraging proteomic data from the UK Biobank, 26 potential AUD-associated biomarkers and 9 prospective ethanol-responsive biomarkers were identified. Crucially, the study also revealed that significant fluctuations in proteomic profiles were strongly correlated with the presence of AUD polygenic scores. This research illuminates unique proteomic fingerprints associated with inherited susceptibility to AUD and alcohol exposure, offering fresh perspectives on the underlying mechanisms of AUD and identifying promising candidate circulating biomarkers for further scrutiny.",
  "summary": "Genome-wide association studies of alcohol use disorder (AUD) have identified >100 loci, yet the functional impact and the downstream molecular mechanisms are not well understood. As functional effectors of genes, proteins provide direct insight into disease mechanisms. However, most proteomic alterations in postmortem human brains of AUD likely reflect a combination of inherited susceptibility…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}