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

Autor: Holen B; NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway. Electronic address: borge.holen@medisin.uio.no., Kutrolli G; NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway., Shadrin AA; NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway., Icick R; 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., Hindley G; NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway., Rødevand L; NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway., O'Connell KS; NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway., Frei O; NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway., Parker N; NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway., Tesfaye M; 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., Deak JD; Yale School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare Center, West Haven, CT, USA., Jahołkowski P; NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway., Dale AM; 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., Djurovic S; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway., Andreassen OA; NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway., Smeland OB; NORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0407, Norway. Electronic address: o.b.smeland@medisin.uio.no.
Jazyk: angličtina
Zdroj: Drug and alcohol dependence [Drug Alcohol Depend] 2024 Mar 01; Vol. 256, pp. 111058. Date of Electronic Publication: 2023 Dec 11.
DOI: 10.1016/j.drugalcdep.2023.111058
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest OAA has received speaker’s honoraria from Sunovion, Lundbeck and Janssen and is a consultant for Cortechs.ai. AMD is a founder of and holds equity interest in CorTechs Labs and serves on its scientific advisory board. He is also a member of the Scientific Advisory Board of Healthlytix and receives research funding from General Electric Healthcare (GEHC). The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. JG is a named inventor on PCT patent application #15/878,640 entitled: "Genotype-guided dosing of opioid agonists," filed January 24, 2018 and issued on January 26, 2021 as U.S. Patent No. 10,900,082. JG was paid for editorial work on the journal Complex Psychiatry. Remaining authors have no conflicts of interest to declare.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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