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Epigenetic alterations identify a confluence of genetic vulnerabilities tied to opioid overdose

Neuropsychopharmacology volume 49, pages 333–334 (2024)Cite this article

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Opioid use disorder (OUD) is a complex, multifactorial disorder that has had widespread impact on communities nationwide [1]. The etiology of OUD is defined by both heritable [2, 3] and environmental risk factors such as early life adversity and socioeconomic status [4]. The most severe outcome of OUD, opioid overdose, has become the leading cause of accidental death in the US [5]. Epigenetic studies have the potential to further understanding of this complex trait by directly assaying patient tissues. These studies can reveal a snapshot of the combined genetic and environmental influences on gene regulation that occurs throughout the course of disease.

Recently, epigenetic studies of opioid overdose have utilized H3K27ac chromatin profiling to identify key epigenetic changes that distinguish individuals who died from opioid overdose [6]. H3K27ac is a marker of active enhancers and promoters and thus is a highly cell type and tissue specific measure of changes in gene regulation. In this study, neurons were isolated from the dorsolateral prefrontal cortex from 51 opioid overdose cases and 51 sudden death controls, excluding all samples that were comorbid for neuropsychiatric disorders. Using standard strategies, 388 loci were identified with altered histone acetylation in opioid overdose cases. These loci had a modest but consistent reduction in acetylation across opioid cases, suggesting a reduction in enhancer activity. These peaks were enriched near genes in the MAPK pathway and other genes previously implicated in opioid addiction.

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Fig. 1: Diagram of chromatin studies.

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Acknowledgements

We thank Schahram Akbarian, Eric O. Johnson, Peter Scacheri and Richard Sallari for helpful discussion and insights in the development of this work.

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  1. Whitehead Institute for Biomedical Research, Cambridge, MA, USA

    An T. Hoang & Olivia Corradin

  2. Massachusetts Institute of Technology, Department of Biology, Cambridge, MA, USA

    Olivia Corradin

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  1. An T. Hoang
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ATH and OC wrote, edited, and approved the article.

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Correspondence to Olivia Corradin.

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Hoang, A.T., Corradin, O. Epigenetic alterations identify a confluence of genetic vulnerabilities tied to opioid overdose. Neuropsychopharmacol. 49, 333–334 (2024). https://doi.org/10.1038/s41386-023-01701-5

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