Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
36207451
TITLE
Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond.
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 (r  > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10 ). 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.
© 2022. The Author(s).
DATE PUBLISHED
2022 Oct 07
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2022/07/27
accepted 2022/09/21
entrez 2022/10/07 23:31
pubmed 2022/10/08 06:00
medline 2022/10/12 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Gaddis N Gaddis Nathan N GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
Mathur R Mathur Ravi R GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
Marks J Marks Jesse J GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
Zhou L Zhou Linran L GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
Quach B Quach Bryan B GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
Waldrop A Waldrop Alex A GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
Levran O Levran Orna O The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
Agrawal A Agrawal Arpana A Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Randesi M Randesi Matthew M The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
Adelson M Adelson Miriam M Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse, Treatment and Research, Las Vegas, NV, USA.
Jeffries PW Jeffries Paul W PW Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Martin NG Martin Nicholas G NG Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Degenhardt L Degenhardt Louisa L National Drug and Alcohol Research Centre, University of New South Wales, Randwick, NSW, Australia.
Montgomery GW Montgomery Grant W GW Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Wetherill L Wetherill Leah L Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Lai D Lai Dongbing D Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Bucholz K Bucholz Kathleen K Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Foroud T Foroud Tatiana T Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Porjesz B Porjesz Bernice B Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
Runarsdottir V Runarsdottir Valgerdur V SAA-National Center of Addiction Medicine, Vogur Hospital, Reykjavik, Iceland.
Tyrfingsson T Tyrfingsson Thorarinn T SAA-National Center of Addiction Medicine, Vogur Hospital, Reykjavik, Iceland.
Einarsson G Einarsson Gudmundur G deCODE Genetics/Amgen, Reykjavik, Iceland.
Gudbjartsson DF Gudbjartsson Daniel F DF deCODE Genetics/Amgen, Reykjavik, Iceland.
Webb BT Webb Bradley Todd BT GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
Crist RC Crist Richard C RC Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Kranzler HR Kranzler Henry R HR Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Sherva R Sherva Richard R Genome Science Institute, Boston University, Boston, MA, USA.
Zhou H Zhou Hang H Department of Psychiatry, Yale University School of Medicine, West Haven, CT, USA.
Hulse G Hulse Gary G School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, WA, Australia.
Wildenauer D Wildenauer Dieter D School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, WA, Australia.
Kelty E Kelty Erin E School of Population and Global Health, Population and Public Health, The University of Western Australia, Perth, WA, Australia.
Attia J Attia John J Hunter Medical Research Institute, Newcastle, Australia.
Holliday EG Holliday Elizabeth G EG School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW, Australia.
McEvoy M McEvoy Mark M School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW, Australia.
Scott RJ Scott Rodney J RJ School of Biomedical Sciences and Pharmacy College of Health, Medicine and Wellbeing, The University of Newcastle, New Lambton Heights, NSW, Australia.
Schwab SG Schwab Sibylle G SG Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, Australia.
Maher BS Maher Brion S BS Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Gruza R Gruza Richard R Department of Family and Community Medicine, Saint Louis University, Saint Louis, MO, USA.
Kreek MJ Kreek Mary Jeanne MJ The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
Nelson EC Nelson Elliot C EC Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Thorgeirsson T Thorgeirsson Thorgeir T deCODE Genetics/Amgen, Reykjavik, Iceland.
Stefansson K Stefansson Kari K Faculty of Medicine, University of Iceland, Reyjavik, Iceland.
Berrettini WH Berrettini Wade H WH Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Gelernter J Gelernter Joel J Department of Psychiatry, Genetics, & Neuroscience, Yale University School of Medicine, West Haven, CT, USA.
Edenberg HJ Edenberg Howard J HJ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Bierut L Bierut Laura L Department of Psychiatry, Washington University, St. Louis, MO, USA.
Hancock DB Hancock Dana B DB GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
Johnson EO Johnson Eric Otto EO Fellow Program, RTI International, Research Triangle Park, NC, USA. ejohnson@rti.org.
INVESTIGATORS
JOURNAL
VOLUME: 12
ISSUE: 1
TITLE: Scientific reports
ISOABBREVIATION: Sci Rep
YEAR: 2022
MONTH: Oct
DAY: 07
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2045-2322
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Sci Rep
COUNTRY: England
ISSNLINKING: 2045-2322
NLMUNIQUEID: 101563288
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
R01DA044014 NIDA NIH HHS United States
R01DA038632 NIDA NIH HHS United States
R33DA027486 NIDA NIH HHS United States
K01DA036751 NIDA NIH HHS United States
R01DA04401 NIDA NIH HHS United States
U10AA008401 NIAAA NIH HHS United States
H2020-2020-848099 European Commission to the painFACT project
non-formulary grant Pharmacogenetics of Opioid Use Disorder Pennsylvania State Department of Health Tobacco Settlement
UL1RR024143 NCATS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Furin genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
Humans genetics
Opioid-Related Disorders genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
Receptors, Opioid, mu genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 OPRM1 protein, human
0 Receptors, Opioid, mu
EC 3.4.21.75 Furin
OTHER ID's
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