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Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond.
Gaddis, Nathan; Mathur, Ravi; Marks, Jesse; Zhou, Linran; Quach, Bryan; Waldrop, Alex; Levran, Orna; Agrawal, Arpana; Randesi, Matthew; Adelson, Miriam; Jeffries, Paul W; Martin, Nicholas G; Degenhardt, Louisa; Montgomery, Grant W; Wetherill, Leah; Lai, Dongbing; Bucholz, Kathleen; Foroud, Tatiana; Porjesz, Bernice; Runarsdottir, Valgerdur; Tyrfingsson, Thorarinn; Einarsson, Gudmundur; Gudbjartsson, Daniel F; Webb, Bradley Todd; Crist, Richard C; Kranzler, Henry R; Sherva, Richard; Zhou, Hang; Hulse, Gary; Wildenauer, Dieter; Kelty, Erin; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Schwab, Sibylle G; Maher, Brion S; Gruza, Richard; Kreek, Mary Jeanne; Nelson, Elliot C; Thorgeirsson, Thorgeir; Stefansson, Kari; Berrettini, Wade H; Gelernter, Joel; Edenberg, Howard J; Bierut, Laura; Hancock, Dana B; Johnson, Eric Otto.
Afiliação
  • Gaddis N; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
  • Mathur R; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
  • Marks J; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
  • Zhou L; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
  • Quach B; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
  • Waldrop A; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
  • Levran O; The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
  • Agrawal A; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
  • Randesi M; The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
  • Adelson M; Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse, Treatment and Research, Las Vegas, NV, USA.
  • Jeffries PW; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
  • Martin NG; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Degenhardt L; National Drug and Alcohol Research Centre, University of New South Wales, Randwick, NSW, Australia.
  • Montgomery GW; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
  • Wetherill L; Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Lai D; Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Bucholz K; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
  • Foroud T; Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Porjesz B; Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
  • Runarsdottir V; SAA-National Center of Addiction Medicine, Vogur Hospital, Reykjavik, Iceland.
  • Tyrfingsson T; SAA-National Center of Addiction Medicine, Vogur Hospital, Reykjavik, Iceland.
  • Einarsson G; deCODE Genetics/Amgen, Reykjavik, Iceland.
  • Gudbjartsson DF; deCODE Genetics/Amgen, Reykjavik, Iceland.
  • Webb BT; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
  • Crist RC; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
  • Kranzler HR; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
  • Sherva R; Genome Science Institute, Boston University, Boston, MA, USA.
  • Zhou H; Department of Psychiatry, Yale University School of Medicine, West Haven, CT, USA.
  • Hulse G; School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, WA, Australia.
  • Wildenauer D; School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, WA, Australia.
  • Kelty E; School of Population and Global Health, Population and Public Health, The University of Western Australia, Perth, WA, Australia.
  • Attia J; Hunter Medical Research Institute, Newcastle, Australia.
  • Holliday EG; Hunter Medical Research Institute, Newcastle, Australia.
  • McEvoy M; School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW, Australia.
  • Scott RJ; Hunter Medical Research Institute, Newcastle, Australia.
  • Schwab SG; School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW, Australia.
  • Maher BS; School of Biomedical Sciences and Pharmacy College of Health, Medicine and Wellbeing, The University of Newcastle, New Lambton Heights, NSW, Australia.
  • Gruza R; Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, Australia.
  • Kreek MJ; Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
  • Nelson EC; Department of Family and Community Medicine, Saint Louis University, Saint Louis, MO, USA.
  • Thorgeirsson T; The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
  • Stefansson K; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
  • Berrettini WH; deCODE Genetics/Amgen, Reykjavik, Iceland.
  • Gelernter J; deCODE Genetics/Amgen, Reykjavik, Iceland.
  • Edenberg HJ; Faculty of Medicine, University of Iceland, Reyjavik, Iceland.
  • Bierut L; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
  • Hancock DB; Department of Psychiatry, Genetics, & Neuroscience, Yale University School of Medicine, West Haven, CT, USA.
  • Johnson EO; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Sci Rep ; 12(1): 16873, 2022 10 07.
Article em En | MEDLINE | ID: mdl-36207451
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estudo de Associação Genômica Ampla / Transtornos Relacionados ao Uso de Opioides Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estudo de Associação Genômica Ampla / Transtornos Relacionados ao Uso de Opioides Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article