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Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.
Liu, Mengzhen; Jiang, Yu; Wedow, Robbee; Li, Yue; Brazel, David M; Chen, Fang; Datta, Gargi; Davila-Velderrain, Jose; McGuire, Daniel; Tian, Chao; Zhan, Xiaowei; Choquet, Hélène; Docherty, Anna R; Faul, Jessica D; Foerster, Johanna R; Fritsche, Lars G; Gabrielsen, Maiken Elvestad; Gordon, Scott D; Haessler, Jeffrey; Hottenga, Jouke-Jan; Huang, Hongyan; Jang, Seon-Kyeong; Jansen, Philip R; Ling, Yueh; Mägi, Reedik; Matoba, Nana; McMahon, George; Mulas, Antonella; Orrù, Valeria; Palviainen, Teemu; Pandit, Anita; Reginsson, Gunnar W; Skogholt, Anne Heidi; Smith, Jennifer A; Taylor, Amy E; Turman, Constance; Willemsen, Gonneke; Young, Hannah; Young, Kendra A; Zajac, Gregory J M; Zhao, Wei; Zhou, Wei; Bjornsdottir, Gyda; Boardman, Jason D; Boehnke, Michael; Boomsma, Dorret I; Chen, Chu; Cucca, Francesco; Davies, Gareth E; Eaton, Charles B.
Afiliación
  • Liu M; Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
  • Jiang Y; Department of Public Health Sciences, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
  • Wedow R; Institute of Personalized Medicine, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
  • Li Y; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
  • Brazel DM; Department of Sociology, University of Colorado Boulder, Boulder, CO, USA.
  • Chen F; Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO, USA.
  • Datta G; Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Davila-Velderrain J; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • McGuire D; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
  • Tian C; Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, USA.
  • Zhan X; Interdisciplinary Quantitative Biology Graduate Group, University of Colorado Boulder, Boulder, CO, USA.
  • Choquet H; Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
  • Docherty AR; Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Faul JD; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Foerster JR; Department of Public Health Sciences, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
  • Fritsche LG; Institute of Personalized Medicine, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
  • Gabrielsen ME; 23andMe, Inc., Mountain View, CA, USA.
  • Gordon SD; Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Haessler J; Center for the Genetics of Host Defense, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Jang SK; Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
  • Jansen PR; Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
  • Ling Y; Department of Psychiatry and Human Genetics, University of Utah, Salt Lake City, UT, USA.
  • Mägi R; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
  • Matoba N; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  • McMahon G; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Mulas A; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
  • Orrù V; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Palviainen T; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Pandit A; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • Reginsson GW; Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Skogholt AH; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Smith JA; Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
  • Taylor AE; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
  • Turman C; Department of Child and Adolescent Psychiatry, Erasmus MC Rotterdam, Rotterdam, the Netherlands.
  • Willemsen G; Department of Public Health Sciences, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
  • Young H; Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, USA.
  • Young KA; Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Zajac GJM; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama City, Japan.
  • Zhao W; Department of Population Health Science, Bristol Medical School, Oakfield Grove, Bristol, UK.
  • Zhou W; Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato, Italy.
  • Bjornsdottir G; Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato, Italy.
  • Boardman JD; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Boehnke M; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Boomsma DI; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Chen C; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
  • Cucca F; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
  • Davies GE; Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
  • Eaton CB; Department of Population Health Science, Bristol Medical School, Oakfield Grove, Bristol, UK.
Nat Genet ; 51(2): 237-244, 2019 02.
Article en En | MEDLINE | ID: mdl-30643251
ABSTRACT
Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tabaquismo / Consumo de Bebidas Alcohólicas / Fumar Tipo de estudio: Etiology_studies / Risk_factors_studies / Systematic_reviews Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tabaquismo / Consumo de Bebidas Alcohólicas / Fumar Tipo de estudio: Etiology_studies / Risk_factors_studies / Systematic_reviews Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos