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Genome-wide analyses reveal shared genetic architecture and novel risk loci between opioid use disorder and general cognitive ability.

Author information

Affiliations

  • 1. NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway.
      Authors
    • Holen B 1
    • Kutrolli G 1
    • Shadrin AA 1
    • Hindley G 1
    • Rødevand L 1
    • O'Connell KS 1
    • Frei O 1
    • Parker N 1
    • Jahołkowski P 1
    • Andreassen OA 1
    • Smeland OB 1
    (11 authors)
  • 2. NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway; INSERM UMR-S1144, Université Paris Cité, F-75006, France.
      Authors
    • Icick R 2
    (1 author)
  • 3. NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway; NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
      Authors
    • Tesfaye M 3
    (1 author)
  • 4. Yale School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare Center, West Haven, CT, USA.
      Authors
    • Deak JD 4
    (1 author)
  • 5. Department of Radiology, University of California San Diego, La Jolla, CA 92093, USA; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA 92093, USA; Department of Cognitive Science, University of California San Diego, La Jolla, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA.
      Authors
    • Dale AM 5
    (1 author)
    • Show all (6)

ORCIDs linked to this article

Drug and Alcohol Dependence, 11 Dec 2023, 256:111058
https://doi.org/10.1016/j.drugalcdep.2023.111058 PMID: 38244365 

Abstract 

Background

Opioid use disorder (OUD), a serious health burden worldwide, is associated with lower cognitive function. Recent studies have demonstrated a negative genetic correlation between OUD and general cognitive ability (COG), indicating a shared genetic basis. However, the specific genetic variants involved, and the underlying molecular mechanisms remain poorly understood. Here, we aimed to quantify and identify the genetic basis underlying OUD and COG.

Methods

We quantified the extent of genetic overlap between OUD and COG using a bivariate causal mixture model (MiXeR) and identified specific genetic loci applying conditional/conjunctional FDR. Finally, we investigated biological function and expression of implicated genes using available resources.

Results

We estimated that ~94% of OUD variants (4.8k out of 5.1k variants) also influence COG. We identified three novel OUD risk loci and one locus shared between OUD and COG. Loci identified implicated biological substrates in the basal ganglia.

Conclusion

We provide new insights into the complex genetic risk architecture of OUD and its genetic relationship with COG.

Full text links 

Read article at publisher's site: https://doi.org/10.1016/j.drugalcdep.2023.111058

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Funding 

Funders who supported this work.

Helse Sør-Øst RHF (1)

Horizon 2020 (1)

Horizon 2020 Framework Programme

    Kristian Gerhard Jebsen Foundation

      National Institutes of Health (1)

      Norges Forskningsråd (4)

      Norges Idrettshøgskole

        Universitetet i Oslo (1)