Genome-wide association analysis of opioid use disorder: A novel approach using clinical data.

Autor: Song W; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, United States; Department of Biomedical Informatics, Harvard Medical School, United States; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, United States. Electronic address: wsong@bwh.harvard.edu., Kossowsky J; Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children's Hospital, Harvard Medical School, United States; Division of Clinical Psychology and Psychotherapy, University of Basel, United States., Torous J; Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, United States., Chen CY; Psychiatric and Neurodevelopmental Genetics Unit, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, United States; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, United States., Huang H; Psychiatric and Neurodevelopmental Genetics Unit, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, United States; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, United States., Mukamal KJ; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, United States., Berde CB; Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children's Hospital, Harvard Medical School, United States., Bates DW; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, United States; Partners eCare, Partners HealthCare, United States., Wright A; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, United States; Department of Biomedical Informatics, Harvard Medical School, United States; Department of Biomedical Informatics, Vanderbilt University Medical Center, United States; Partners eCare, Partners HealthCare, United States.
Jazyk: angličtina
Zdroj: Drug and alcohol dependence [Drug Alcohol Depend] 2020 Dec 01; Vol. 217, pp. 108276. Date of Electronic Publication: 2020 Sep 15.
DOI: 10.1016/j.drugalcdep.2020.108276
Abstrakt: Background: Opioid use disorder (OUD) represents a large and pervasive global public health challenge. Previous genetic studies have demonstrated the significant heritability of OUD and identified several single-nucleotide polymorphisms (SNPs) associated with its prevalence.
Methods: In this paper, we conducted a genome-wide association analysis on opioid use disorder that leveraged genetic and clinical data contained in a biobank of 21,310 patients of European ancestry. We identified 1039 cases of opioid use disorder based on diagnostic codes from nearly 16 million encounters in electronic health records (EHRs).
Results: We discovered one novel OUD-associated locus on chromosome 4 that was significant at a genome-wide threshold (p = 2.40 × 10 -8 ). Heritability analysis suggested that common SNPs explained 0.06 (se 0.02, p = 0.0065) of the phenotypic variation in OUD. When we restricted controls to those with previous opioid prescriptions, we were able to further strengthen the original signal and discovered another significant locus on chromosome 16. Pair-wise genetic correlation analysis yielded strong positive correlations between OUD and two other major substance use disorders, alcohol and nicotine, with the strongest correlation between nicotine and opioid use disorder (genetic correlation 0.65, se = 0.19, p = 0.00048), suggesting a significant shared genetic component across different substance disorders.
Conclusions: This pragmatic, clinically-focused approach may supplement more traditional methods to facilitate identification of new genetic underpinnings of OUD and related disorders.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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