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Genetic and non-genetic predictors of risk for opioid dependence

Published online by Cambridge University Press:  06 February 2024

Peter J. Na Open the ORCID record for Peter J. Na [Opens in a new window] ,
Joseph D. Deak Open the ORCID record for Joseph D. Deak [Opens in a new window] ,
Henry R. Kranzler Open the ORCID record for Henry R. Kranzler [Opens in a new window] ,
Robert H. Pietrzak Open the ORCID record for Robert H. Pietrzak [Opens in a new window]  and
Joel Gelernter Open the ORCID record for Joel Gelernter [Opens in a new window]
Peter J. Na
Affiliation:
VA Connecticut Healthcare System, West Haven, CT, USA Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
Joseph D. Deak
Affiliation:
VA Connecticut Healthcare System, West Haven, CT, USA Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
Henry R. Kranzler
Affiliation:
Mental Illness Research, Education and Clinical Center, Veterans Integrated Service Network 4, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
Robert H. Pietrzak
Affiliation:
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA Department of Social and Behavioral Sciences, Yale School of Public Health, New Haven, CT, USA
Joel Gelernter*
Affiliation:
VA Connecticut Healthcare System, West Haven, CT, USA Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
*
Corresponding author: Joel Gelernter; Email: joel.gelernter@yale.edu
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Abstract

Background

Elucidation of the interaction of biological and psychosocial/environmental factors on opioid dependence (OD) risk can inform our understanding of the etiology of OD. We examined the role of psychosocial/environmental factors in moderating polygenic risk for opioid use disorder (OUD).

Methods

Data from 1958 European ancestry adults who participated in the Yale-Penn 3 study were analyzed. Polygenic risk scores (PRS) were based on a large-scale multi-trait analysis of genome-wide association studies (MTAG) of OUD.

Results

A total of 420 (21.1%) individuals had a lifetime diagnosis of OD. OUD PRS were positively associated with OD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.21–1.66). Household income and education were the strongest correlates of OD. Among individuals with higher OUD PRS, those with higher education level had lower odds of OD (OR 0.92, 95% CI 0.85–0.98); and those with posttraumatic stress disorder (PTSD) were more likely to have OD relative to those without PTSD (OR 1.56, 95% CI 1.04–2.35).

Conclusions

Results suggest an interplay between genetics and psychosocial environment in contributing to OD risk. While PRS alone do not yet have useful clinical predictive utility, psychosocial factors may help enhance prediction. These findings could inform more targeted clinical and policy interventions to help address this public health crisis.

Keywords

epidemiologyopioidsopioid dependenceopioid use disorderpolygenic risk scoresrisk prediction
Type
Original Article
Information
Psychological Medicine , First View , pp. 1 - 8
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Copyright
Copyright © The Author(s), 2024. Published by Cambridge University Press

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Footnotes

*

PJN and JDD are co-first authors.

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