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Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits.
Quach, Bryan C; Bray, Michael J; Gaddis, Nathan C; Liu, Mengzhen; Palviainen, Teemu; Minica, Camelia C; Zellers, Stephanie; Sherva, Richard; Aliev, Fazil; Nothnagel, Michael; Young, Kendra A; Marks, Jesse A; Young, Hannah; Carnes, Megan U; Guo, Yuelong; Waldrop, Alex; Sey, Nancy Y A; Landi, Maria T; McNeil, Daniel W; Drichel, Dmitriy; Farrer, Lindsay A; Markunas, Christina A; Vink, Jacqueline M; Hottenga, Jouke-Jan; Iacono, William G; Kranzler, Henry R; Saccone, Nancy L; Neale, Michael C; Madden, Pamela; Rietschel, Marcella; Marazita, Mary L; McGue, Matthew; Won, Hyejung; Winterer, Georg; Grucza, Richard; Dick, Danielle M; Gelernter, Joel; Caporaso, Neil E; Baker, Timothy B; Boomsma, Dorret I; Kaprio, Jaakko; Hokanson, John E; Vrieze, Scott; Bierut, Laura J; Johnson, Eric O; Hancock, Dana B.
Afiliação
  • Quach BC; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, 27709, USA.
  • Bray MJ; Department of Psychiatry, Washington University, St. Louis, MO, 63130, USA.
  • Gaddis NC; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, 27709, USA.
  • Liu M; Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, 55455, USA.
  • Palviainen T; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290, Helsinki, Finland.
  • Minica CC; Department of Biological Psychology, Vrije Universiteit, 1081 BT, Amsterdam, The Netherlands.
  • Zellers S; Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, 55455, USA.
  • Sherva R; Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, 02118, USA.
  • Aliev F; Department of Psychology, Virginia Commonwealth University, Richmond, VA, 23284, USA.
  • Nothnagel M; Faculty of Business, Karabuk University, 78050, Kilavuzlar/Karabük Merkez/Karabük, Turkey.
  • Young KA; Cologne Center for Genomics, University of Cologne, 50931, Köln, Germany.
  • Marks JA; University Hospital Cologne, 50931, Köln, Germany.
  • Young H; Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
  • Carnes MU; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, 27709, USA.
  • Guo Y; Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, 55455, USA.
  • Waldrop A; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, 27709, USA.
  • Sey NYA; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, 27709, USA.
  • Landi MT; GeneCentric Therapeutics, Research Triangle Park, NC, 27709, USA.
  • McNeil DW; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, 27709, USA.
  • Drichel D; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.
  • Farrer LA; Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, 20892, USA.
  • Markunas CA; Department of Psychology, West Virginia University, Morgantown, WV, 26505, USA.
  • Vink JM; Department of Dental Practice and Rural Health, West Virginia University, Morgantown, WV, 26505, USA.
  • Hottenga JJ; Cologne Center for Genomics, University of Cologne, 50931, Köln, Germany.
  • Iacono WG; University Hospital Cologne, 50931, Köln, Germany.
  • Kranzler HR; Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, 02118, USA.
  • Saccone NL; Department of Neurology, Boston University School of Medicine, Boston, MA, 02118, USA.
  • Neale MC; Department of Ophthalmology, Boston University School of Medicine, Boston, MA, 02118, USA.
  • Madden P; Department of Epidemiology, Boston University School of Public Health, Boston, MA, 02118, USA.
  • Rietschel M; Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
  • Marazita ML; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, 27709, USA.
  • McGue M; Behavioural Science Institute, Radboud University, 6500 HE, Nijmegen, The Netherlands.
  • Won H; Department of Biological Psychology, Vrije Universiteit, 1081 BT, Amsterdam, The Netherlands.
  • Winterer G; Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, 55455, USA.
  • Grucza R; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Dick DM; VISN 4 MIRECC, Crescenz VA Medical Center, Philadelphia, PA, 19104, USA.
  • Gelernter J; Department of Genetics, Washington University, St. Louis, MO, 63130, USA.
  • Caporaso NE; Division of Biostatistics, Washington University, St. Louis, MO, 63130, USA.
  • Baker TB; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23284, USA.
  • Boomsma DI; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, 23284, USA.
  • Kaprio J; Department of Psychiatry, Washington University, St. Louis, MO, 63130, USA.
  • Hokanson JE; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Mannheim, Germany.
  • Vrieze S; Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
  • Bierut LJ; Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, 55455, USA.
  • Johnson EO; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.
  • Hancock DB; Experimental & Clinical Research Center, Department of Anesthesiology and Operative Intensive Care Medicine, Charité - University Medicine Berlin, 10117, Berlin, Germany.
Nat Commun ; 11(1): 5562, 2020 11 03.
Article em En | MEDLINE | ID: mdl-33144568
ABSTRACT
Cigarette smoking is the leading cause of preventable morbidity and mortality. Genetic variation contributes to initiation, regular smoking, nicotine dependence, and cessation. We present a Fagerström Test for Nicotine Dependence (FTND)-based genome-wide association study in 58,000 European or African ancestry smokers. We observe five genome-wide significant loci, including previously unreported loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416), and extend loci reported for other smoking traits to nicotine dependence. Using the heaviness of smoking index from UK Biobank (N = 33,791), rs2714700 is consistently associated; rs1862416 is not associated, likely reflecting nicotine dependence features not captured by the heaviness of smoking index. Both variants influence nearby gene expression (rs2714700/MAGI2-AS3 in hippocampus; rs1862416/TENM2 in lung), and expression of genes spanning nicotine dependence-associated variants is enriched in cerebellum. Nicotine dependence (SNP-based heritability = 8.6%) is genetically correlated with 18 other smoking traits (rg = 0.40-1.09) and co-morbidities. Our results highlight nicotine dependence-specific loci, emphasizing the FTND as a composite phenotype that expands genetic knowledge of smoking.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tabagismo / Característica Quantitativa Herdável / Predisposição Genética para Doença Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tabagismo / Característica Quantitativa Herdável / Predisposição Genética para Doença Idioma: En Ano de publicação: 2020 Tipo de documento: Article