Scientific Reports (Oct 2022)
Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond
- Nathan Gaddis,
- Ravi Mathur,
- Jesse Marks,
- Linran Zhou,
- Bryan Quach,
- Alex Waldrop,
- Orna Levran,
- Arpana Agrawal,
- Matthew Randesi,
- Miriam Adelson,
- Paul W. Jeffries,
- Nicholas G. Martin,
- Louisa Degenhardt,
- Grant W. Montgomery,
- Leah Wetherill,
- Dongbing Lai,
- Kathleen Bucholz,
- Tatiana Foroud,
- Bernice Porjesz,
- Valgerdur Runarsdottir,
- Thorarinn Tyrfingsson,
- Gudmundur Einarsson,
- Daniel F. Gudbjartsson,
- Bradley Todd Webb,
- Richard C. Crist,
- Henry R. Kranzler,
- Richard Sherva,
- Hang Zhou,
- Gary Hulse,
- Dieter Wildenauer,
- Erin Kelty,
- John Attia,
- Elizabeth G. Holliday,
- Mark McEvoy,
- Rodney J. Scott,
- Sibylle G. Schwab,
- Brion S. Maher,
- Richard Gruza,
- Mary Jeanne Kreek,
- Elliot C. Nelson,
- Thorgeir Thorgeirsson,
- Kari Stefansson,
- Wade H. Berrettini,
- Joel Gelernter,
- Howard J. Edenberg,
- Laura Bierut,
- Dana B. Hancock,
- Eric Otto Johnson
Affiliations
- Nathan Gaddis
- GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International
- Ravi Mathur
- GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International
- Jesse Marks
- GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International
- Linran Zhou
- GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International
- Bryan Quach
- GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International
- Alex Waldrop
- GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International
- Orna Levran
- The Laboratory of the Biology of Addictive Diseases, The Rockefeller University
- Arpana Agrawal
- Department of Psychiatry, Washington University School of Medicine
- Matthew Randesi
- The Laboratory of the Biology of Addictive Diseases, The Rockefeller University
- Miriam Adelson
- Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse, Treatment and Research
- Paul W. Jeffries
- Department of Psychiatry, Washington University School of Medicine
- Nicholas G. Martin
- Genetic Epidemiology, QIMR Berghofer Medical Research Institute
- Louisa Degenhardt
- National Drug and Alcohol Research Centre, University of New South Wales
- Grant W. Montgomery
- Institute for Molecular Bioscience, The University of Queensland
- Leah Wetherill
- Medical and Molecular Genetics, Indiana University School of Medicine
- Dongbing Lai
- Medical and Molecular Genetics, Indiana University School of Medicine
- Kathleen Bucholz
- Department of Psychiatry, Washington University School of Medicine
- Tatiana Foroud
- Medical and Molecular Genetics, Indiana University School of Medicine
- Bernice Porjesz
- Department of Psychiatry, State University of New York Downstate Medical Center
- Valgerdur Runarsdottir
- SAA-National Center of Addiction Medicine, Vogur Hospital
- Thorarinn Tyrfingsson
- SAA-National Center of Addiction Medicine, Vogur Hospital
- Gudmundur Einarsson
- deCODE Genetics/Amgen
- Daniel F. Gudbjartsson
- deCODE Genetics/Amgen
- Bradley Todd Webb
- GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International
- Richard C. Crist
- Department of Psychiatry, University of Pennsylvania
- Henry R. Kranzler
- Department of Psychiatry, University of Pennsylvania
- Richard Sherva
- Genome Science Institute, Boston University
- Hang Zhou
- Department of Psychiatry, Yale University School of Medicine
- Gary Hulse
- School of Psychiatry and Clinical Neurosciences, The University of Western Australia
- Dieter Wildenauer
- School of Psychiatry and Clinical Neurosciences, The University of Western Australia
- Erin Kelty
- School of Population and Global Health, Population and Public Health, The University of Western Australia
- John Attia
- Hunter Medical Research Institute
- Elizabeth G. Holliday
- Hunter Medical Research Institute
- Mark McEvoy
- Hunter Medical Research Institute
- Rodney J. Scott
- School of Biomedical Sciences and Pharmacy College of Health, Medicine and Wellbeing, The University of Newcastle
- Sibylle G. Schwab
- Faculty of Science, Medicine and Health, University of Wollongong
- Brion S. Maher
- Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University
- Richard Gruza
- Department of Family and Community Medicine, Saint Louis University
- Mary Jeanne Kreek
- The Laboratory of the Biology of Addictive Diseases, The Rockefeller University
- Elliot C. Nelson
- Department of Psychiatry, Washington University School of Medicine
- Thorgeir Thorgeirsson
- deCODE Genetics/Amgen
- Kari Stefansson
- deCODE Genetics/Amgen
- Wade H. Berrettini
- Department of Psychiatry, University of Pennsylvania
- Joel Gelernter
- Department of Psychiatry, Genetics, & Neuroscience, Yale University School of Medicine
- Howard J. Edenberg
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine
- Laura Bierut
- Department of Psychiatry, Washington University
- Dana B. Hancock
- GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International
- Eric Otto Johnson
- GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International
- DOI
- https://doi.org/10.1038/s41598-022-21003-y
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 16
Abstract
Abstract Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10–9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.
