Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

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  • Liu, M.
    • Other Affiliation: University of Minnesota Twin Cities
  • Jiang, Y.
    • Other Affiliation: Pennsylvania State University
  • Wedow, R.
    • Other Affiliation: University of Colorado Boulder
  • Li, Y.
    • Other Affiliation: The Broad Institute of MIT and Harvard
  • Brazel, D.M.
    • Other Affiliation: University of Colorado Boulder
  • Chen, F.
    • Other Affiliation: Pennsylvania State University
  • Datta, G.
    • Other Affiliation: University of Minnesota Twin Cities
  • Davila-Velderrain, J.
    • Other Affiliation: The Broad Institute of MIT and Harvard
  • McGuire, D.
    • Other Affiliation: Pennsylvania State University
  • Tian, C.
    • Other Affiliation: 23andMe, Inc.
  • Zhan, X.
    • Other Affiliation: University of Texas Southwestern Medical Center
  • 23andMe Research Team
  • HUNT All-In Psychiatry
  • Choquet, H.
    • Other Affiliation: Kaiser Permanente Northern California
  • Docherty, A.R.
    • Other Affiliation: Virginia Commonwealth University
  • Faul, J.D.
    • Other Affiliation: University of Michigan
  • Foerster, J.R.
    • Other Affiliation: University of Michigan
  • Fritsche, L.G.
    • Other Affiliation: University of Michigan
  • Gordon, S.D.
    • Other Affiliation: QIMR Berghofer Medical Research Institute
  • Haessler, J.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Hottenga, J.-J.
    • Other Affiliation: Vrije Universiteit Amsterdam
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    • Other Affiliation: Harvard T.H. Chan School of Public Health
  • Jang, S.-K.
    • Other Affiliation: University of Minnesota Twin Cities
  • Jansen, P.R.
    • Other Affiliation: Vrije Universiteit Amsterdam
  • Ling, Y.
    • Other Affiliation: Pennsylvania State University
  • Mägi, R.
    • Other Affiliation: University of Tartu
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    • Other Affiliation: RIKEN Center for Integrative Medical Sciences
  • McMahon, G.
    • Other Affiliation: Bristol Medical School
  • Mulas, A.
    • Other Affiliation: Consiglio Nazionale delle Ricerche
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    • Other Affiliation: Consiglio Nazionale delle Ricerche
  • Palviainen, T.
    • Other Affiliation: University of Helsinki
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    • Other Affiliation: University of Michigan
  • Reginsson, G.W.
    • Other Affiliation: deCODE Genetics/Amgen, Inc.
  • Smith, J.A.
    • Other Affiliation: University of Michigan
  • Taylor, A.E.
    • Other Affiliation: Bristol Medical School
  • Turman, C.
    • Other Affiliation: Harvard T.H. Chan School of Public Health
  • Willemsen, G.
    • Other Affiliation: Vrije Universiteit Amsterdam
  • Young, H.
    • Other Affiliation: University of Minnesota Twin Cities
  • Young, K.A.
    • Other Affiliation: University of Colorado Anschutz Medical Campus
  • Zajac, G.J.M.
    • Other Affiliation: University of Michigan
  • Zhao, W.
    • Other Affiliation: University of Michigan
  • Zhou, W.
    • Other Affiliation: University of Michigan
  • Bjornsdottir, G.
    • Other Affiliation: deCODE Genetics/Amgen, Inc.
  • Boardman, J.D.
    • Other Affiliation: University of Colorado Boulder
  • Boehnke, M.
    • Other Affiliation: University of Michigan
  • Boomsma, D.I.
    • Other Affiliation: Vrije Universiteit Amsterdam
  • Chen, C.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Cucca, F.
    • Other Affiliation: Consiglio Nazionale delle Ricerche
  • Davies, G.E.
    • Other Affiliation: Avera Institute for Human Genetics
  • Eaton, C.B.
    • Other Affiliation: Brown University
  • Ehringer, M.A.
    • Other Affiliation: University of Colorado Boulder
  • Esko, T.
    • Other Affiliation: University of Tartu
  • Fiorillo, E.
    • Other Affiliation: Consiglio Nazionale delle Ricerche
  • Gillespie, N.A.
    • Other Affiliation: Virginia Commonwealth University
  • Gudbjartsson, D.F.
    • Other Affiliation: University of Iceland
  • Haller, T.
    • Other Affiliation: University of Tartu
  • Harris, K.M.
    • College of Arts and Sciences, Department of Sociology
  • Heath, A.C.
    • Other Affiliation: Washington University in St. Louis
  • Hewitt, J.K.
    • Other Affiliation: University of Colorado Boulder
  • Hickie, I.B.
    • Other Affiliation: University of Sydney
  • Hokanson, J.E.
    • Other Affiliation: University of Colorado Anschutz Medical Campus
  • Hopfer, C.J.
    • Other Affiliation: University of Colorado Boulder
  • Hunter, D.J.
    • Other Affiliation: Harvard T.H. Chan School of Public Health
  • Iacono, W.G.
    • Other Affiliation: University of Minnesota Twin Cities
  • Johnson, E.O.
    • Other Affiliation: RTI International
  • Kamatani, Y.
    • Other Affiliation: RIKEN Center for Integrative Medical Sciences
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    • Other Affiliation: University of Michigan
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    • Other Affiliation: The Broad Institute of MIT and Harvard
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    • Other Affiliation: Fred Hutchinson Cancer Research Center
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    • Other Affiliation: University of Colorado Boulder
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    • Other Affiliation: Kuopio University Hospital
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    • Other Affiliation: QIMR Berghofer Medical Research Institute
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    • Other Affiliation: University of Helsinki
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    • Other Affiliation: University of Colorado Anschutz Medical Campus
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    • Other Affiliation: Washington University in St. Louis
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  • McGue, M.
    • Other Affiliation: University of Minnesota Twin Cities
  • McQueen, M.B.
    • Other Affiliation: University of Colorado Boulder
  • Medland, S.E.
    • Other Affiliation: QIMR Berghofer Medical Research Institute
  • Metspalu, A.
    • Other Affiliation: University of Tartu
  • Mohlke, K.L.
    • School of Medicine, Department of Genetics
  • Nielsen, J.B.
    • Other Affiliation: University of Michigan
  • Okada, Y.
    • Other Affiliation: RIKEN Center for Integrative Medical Sciences
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    • Other Affiliation: University of Washington
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    • Other Affiliation: Vrije Universiteit Amsterdam
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    • Other Affiliation: University of Colorado Boulder
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    • Other Affiliation: University of Eastern Finland
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    • Other Affiliation: deCODE Genetics/Amgen, Inc.
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    • Other Affiliation: Kaiser Permanente Northern California
  • Tindle, H.A.
    • Other Affiliation: Vanderbilt University
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  • Wall, T.L.
    • Other Affiliation: University of California, San Diego
  • Weir, D.R.
    • Other Affiliation: University of Michigan
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    • Other Affiliation: Kaiser Permanente Northern California
  • Whitfield, J.B.
    • Other Affiliation: QIMR Berghofer Medical Research Institute
  • Yin, J.
    • Other Affiliation: Kaiser Permanente Northern California
  • Zuccolo, L.
    • Other Affiliation: University of Bristol
  • Bierut, L.J.
    • Other Affiliation: Washington University School of Medicine
  • Hveem, K.
    • Other Affiliation: Norwegian University of Science and Technology
  • Lee, J.J.
    • Other Affiliation: University of Minnesota Twin Cities
  • Munafò, M.R.
    • Other Affiliation: University of Bristol
  • Saccone, N.L.
    • Other Affiliation: Washington University School of Medicine
  • Willer, C.J.
    • Other Affiliation: University of Michigan
  • Cornelis, M.C.
    • Other Affiliation: Northwestern University Feinberg School of Medicine
  • David, S.P.
    • Other Affiliation: Stanford University School of Medicine
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    • Other Affiliation: Kaiser Permanente Northern California
  • Kaprio, J.
    • Other Affiliation: University of Helsinki
  • Stitzel, J.A.
    • Other Affiliation: University of Colorado Boulder
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    • Other Affiliation: deCODE Genetics/Amgen, Inc.
  • Thorgeirsson, T.E.
    • Other Affiliation: deCODE Genetics/Amgen, Inc.
  • Abecasis, G.
    • Other Affiliation: University of Michigan
  • Liu, D.J.
    • Other Affiliation: ennsylvania State University
  • Vrieze, S.
    • Other Affiliation: University of Minnesota Twin Cities
Abstract
  • Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders. They are heritable and etiologically related behaviors that have been resistant to gene discovery efforts. 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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  • Article
Rights statement
  • In Copyright
Journal title
  • Nature Genetics
Journal volume
  • 51
Journal issue
  • 2
Page start
  • 237
Page end
  • 244
Language
  • English
Version
  • Postprint
ISSN
  • 1061-4036
Publisher
  • Nature Publishing Group

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