Nature Genetics

, volume 51 , issue 2 , pages 237-244

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

Mengzhen Liu ¹

Yu Jiang ^{2, 3, 4}

Wedow R ^{5, 6}

Yue Li ^{2, 7, 8}

David M Brazel ^{9, 10}

Fang Chen ¹

Gargi Datta ^{5, 6}

Jose Davila Velderrain ^{9, 10}

Daniel McGuire ¹¹

Chao Tian ^{12, 13}

Xiaowei Zhan ¹⁴

Hélène Choquet ^{15, 16}

Anna R. Docherty ¹⁷

Jessica D. Faul ¹⁸

Johanna R Foerster ¹⁸

Lars Fritsche ¹⁹

Maiken Elvestad Gabrielsen ²⁰

Scott D. Gordon ²¹

Jeffrey Haessler ²²

Jouke-Jan Hottenga ^{23, 24}

Hongyan Huang ¹

Seon-Kyeong Jang ^{25, 26}

Philip R. Jansen ^{7, 9}

Yueh Ling ²⁷

Reedik Mägi ²⁸

Nana Matoba ²⁹

George McMahon ³⁰

Antonella Mulas ³⁰

Valeria Orrù ³¹

Teemu Palviainen ¹⁸

Anita Pandit ³²

Gunnar W. Reginsson ¹⁹

Anne Heidi Skogholt ^{17, 33}

Jennifer A. Smith ²⁹

Amy E. Taylor ^{23, 24}

Constance Turman ²²

Gonneke Willemsen ¹

Hannah Young ³⁴

Kendra A. Young ¹⁸

Gregory J M Zajac ³³

Wei Zhao ³⁵

Wei Zhou ³²

Gyda Bjornsdottir ^{2, 3, 4}

Jason D. Boardman ¹⁸

Michael Boehnke ²²

Dorret I. Boomsma ²¹

Chen Chu ³⁰

Francesco Cucca ³⁶

Gareth E. DAVIES ³⁷

Charles B Eaton ^{2, 38}

Marissa A Ehringer ^{6, 27}

Tõnu Esko ³⁰

Edoardo Fiorillo ^{15, 20}

Nathan A Gillespie ^{32, 39}

Daniel Gudbjartsson ²⁷

Toomas Haller ^{40, 41}

Kathleen Mullan Harris ⁴²

Andrew C Heath ^{2, 43}

John K Hewitt ⁴⁴

Ian B. Hickie ³⁴

John E Hokanson ^{2, 45}

Christian J Hopfer ^{23, 24, 46}

David J. Hunter ¹

William G. Iacono ⁴⁷

Eric O. Johnson ²⁸

Yoichiro Kamatani ³³

Sharon L. R. Kardia ^{2, 43}

Matthew C. Keller ^{5, 6}

Manolis Kellis ²¹

Charles Kooperberg ^{23, 24, 48}

Peter Kraft ^{2, 7}

Kenneth S Krauter ^{49, 50}

Markku Laakso ⁵¹

Penelope A. Lind ³¹

Anu Loukola ⁵²

Sharon M. Lutz ⁴²

Pamela A F Madden ²⁰

Neil A. Martin ¹

Matt McGue ^{2, 38}

Matthew B. McQueen ⁵¹

Sarah E. Medland ²⁷

Andres Metspalu ⁵³

Karen L. Mohlke ⁵⁴

Jonas Nielsen ^{28, 55}

Yukinori Okada ^{21, 56}

Ulrike Peters ²⁵

Tinca J.C. Polderman ^{25, 57}

Danielle Posthuma ^{21, 56}

Alexander P Reiner ⁵⁸

John P. Rice ^{24, 59}

Eric Rimm ⁶⁰

Richard J. Rose ⁶¹

Valgerdur Runarsdottir ^{2, 43}

Michael C Stallings ⁴⁹

Alena Stančáková ³²

Hreinn Stefansson ¹⁴

Khanh K. Thai ⁶²

Hilary A. Tindle ⁶¹

Thorarinn Tyrfingsson ⁶³

Tamara L Wall ¹⁷

David R Weir ¹⁴

Constance Weisner ²⁰

John B. Whitfield ⁶⁴

Bendik S. Winsvold ¹⁴

Jie Yin ^{29, 65}

Luisa Zuccolo ⁵⁸

Laura J. Bierut ^{19, 66, 67}

Kristian Hveem ¹

James J. Lee ^{65, 68}

Marcus R. Munafò ⁶⁹

Nancy L. Saccone ^{35, 54, 70}

Cristen J. Willer ⁷¹

Marilyn C Cornelis ⁷²

Sean P. David ¹¹

David A. Hinds ¹⁴

Eric Jorgenson ^{31, 73}

J Kaprio ^{2, 38}

Jerry A Stitzel ^{32, 74}

Kari Stefansson ³²

Thorgeir E. Thorgeirsson ¹⁸

Goncalo Abecasis ^{9, 10}

Dajiang J Liu ¹

Hide authors affiliations Show authors affiliations: 74 affiliations

Department of Psychology, University of Minnesota Twin Cities, Minneapolis, USA |

Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, USA |

Department of Sociology, University of Colorado Boulder, Boulder, USA |

⁴

Institute of Behavioral Science, University of Colorado Boulder, Boulder, USA |

⁵

Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, Cambridge, USA |

⁶

the Broad Institute of MIT and Harvard, Cambridge, USA |

⁷

Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, USA |

⁸

Interdisciplinary Quantitative Biology Graduate Group, University of Colorado Boulder, Boulder, USA |

⁹

Department of Public Health Sciences, College of Medicine, Pennsylvania State University, Hershey, USA |

¹⁰

Institute of Personalized Medicine, College of Medicine, Pennsylvania State University, Hershey, USA |

¹¹

23andMe, Inc., Mountain View, USA |

¹²

Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, USA |

¹³

Center for the Genetics of Host Defense, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, USA |

¹⁴

Division of Research, Kaiser Permanente Northern California, Oakland, USA |

¹⁵

Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, USA |

¹⁶

Department of Psychiatry and Human Genetics, University of Utah, Salt Lake City, USA |

¹⁷

Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, USA |

¹⁸

Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, USA |

¹⁹

K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway |

²⁰

Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia |

²¹

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA |

²²

Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands |

²³

Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, USA |

²⁴

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA |

²⁵

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands |

²⁶

Department of Child and Adolescent Psychiatry, Erasmus MC Rotterdam, Rotterdam, The Netherlands |

²⁷

Estonian Genome Center, University of Tartu, Tartu, Estonia |

²⁸

Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama City, Japan |

²⁹

Department of Population Health Science, Bristol Medical School, Oakfield Grove, Bristol, UK |

³⁰

Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato, Italy |

³¹

Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

University of Helsinki

Institute for Molecular Medicine Finland

³²

deCODE genetics/Amgen, Inc., Reykjavik, Iceland |

³³

Department of Epidemiology, University of Michigan, Ann Arbor, USA |

³⁴

Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, USA |

³⁵

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, USA |

³⁶

Avera Institute for Human Genetics, Sioux Falls, USA |

³⁷

Department of Family Medicine and Community Health, Alpert Medical School, Brown University, Providence, USA |

³⁸

Department of Integrative Physiology, University of Colorado Boulder, Boulder, USA |

³⁹

School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland |

⁴⁰

Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, USA |

⁴¹

Carolina Population Center, University of North Carolina At Chapel Hill, Chapel Hill, USA |

⁴²

Department of Psychiatry, Washington University in St. Louis, St. Louis, USA |

⁴³

Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, USA |

⁴⁴

Brain and Mind Centre, University of Sydney, Sydney, Australia |

⁴⁵

Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, USA |

⁴⁶

Nuffield Department of Population Health, University of Oxford, Oxford, UK |

⁴⁷

Fellows Program, RTI International, Research Triangle Park, USA |

⁴⁸

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, USA |

⁴⁹

Department of Internal Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland |

⁵⁰

Department of Medicine, Kuopio University Hospital, Kuopio, Finland |

⁵¹

Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia |

⁵²

Department of Biostatistics and Bioinformatics, University of Colorado Anschutz Medical Campus, Aurora, USA |

⁵³

Department of Genetics, University of North Carolina At Chapel Hill, Chapel Hill, USA |

⁵⁴

Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, USA |

⁵⁵

Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan |

⁵⁶

Department of Epidemiology, University of Washington, Seattle, USA |

⁵⁷

Department of Clinical Genetics, VU Medical Centre Amsterdam, Amsterdam, the Netherlands |

⁵⁸

Department of Psychiatry, Washington University School of Medicine, St. Louis, USA |

⁵⁹

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, USA |

⁶⁰

Department of Psychological and Brain Sciences, Indiana University, Bloomington, USA |

⁶¹

SAA—National Center of Addiction Medicine, Vogur Hospital, Reykjavik, Iceland |

⁶²

Department of Medicine, Vanderbilt University, Nashville, USA |

⁶³

Department of Psychiatry, University of California, San Diego, San Diego, USA |

⁶⁴

FORMI and Department of Neurology, Oslo University Hospital, Oslo, Norway |

⁶⁵

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK |

⁶⁶

HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger, Norway |

⁶⁷

Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway |

⁶⁸

UK Centre for Tobacco and Alcohol Studies, School of Psychological Science, University of Bristol, Bristol, UK |

⁶⁹

Department of Genetics, Washington University School of Medicine, St. Louis, USA |

⁷⁰

Department of Human Genetics, University of Michigan, Ann Arbor, USA |

⁷¹

Department of Preventative Medicine, Northwestern University Feinberg School of Medicine, Chicago, USA |

⁷²

Department of Medicine, Stanford University School of Medicine, Stanford, USA |

⁷³

Department of Public health, University of Helsinki, Helsinki, Finland |

⁷⁴

Faculty of medicine, University of Iceland, Reykjavik, Iceland |

Publication type: Journal Article

Publication date: 2019-01-14

Springer Nature

Nature Genetics

scimago Q1

wos Q1

SJR: 16.586

CiteScore: 45.1

Impact factor: 29.0

ISSN: 10614036, 15461718

DOI: 10.1038/s41588-018-0307-5

Copy DOI

PubMed ID: 30643251

Genetics

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. Association studies of up to 1.2 million individuals identify 566 genetic variants in 406 loci associated with tobacco use and addiction (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci showing pleiotropic association.

Found

2 citations

Georgiou Andrea

🥼 🤝

19 publications, 194 citations, 4 reviews

h-index: 10

University of Cyprus

University of Ioannina

2 citations

Carr Jonathan

120 publications, 3 117 citations, 4 reviews

h-index: 30

South African Medical Research Council

Stellenbosch University

Tygerberg Hospital

German Center for Neurodegenerative Diseases

University of Tübingen

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Liu M. et al. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use // Nature Genetics. 2019. Vol. 51. No. 2. pp. 237-244.

GOST all authors (up to 50) Copy

Liu M. et al. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use // Nature Genetics. 2019. Vol. 51. No. 2. pp. 237-244.

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BibTex (up to 50 authors) Copy

@article{2019_Liu,

author = {Mengzhen Liu and Yu Jiang and Wedow R and Yue Li and David M Brazel and Fang Chen and Gargi Datta and Jose Davila Velderrain and Daniel McGuire and Chao Tian and Xiaowei Zhan and Hélène Choquet and Anna R. Docherty and Jessica D. Faul and Johanna R Foerster and Lars Fritsche and Maiken Elvestad Gabrielsen and Scott D. Gordon and Jeffrey Haessler and Jouke-Jan Hottenga and Hongyan Huang and Seon-Kyeong Jang and Philip R. Jansen and Yueh Ling and Reedik Mägi and Nana Matoba and George McMahon and Antonella Mulas and Valeria Orrù and Teemu Palviainen and Anita Pandit and Gunnar W. Reginsson and Anne Heidi Skogholt and Jennifer A. Smith and Amy E. Taylor and Constance Turman and Gonneke Willemsen and Hannah Young and Kendra A. Young and Gregory J M Zajac and Wei Zhao and Wei Zhou and Gyda Bjornsdottir and Jason D. Boardman and Michael Boehnke and Dorret I. Boomsma and Chen Chu and Francesco Cucca and Gareth E. DAVIES and Charles B Eaton and others},

title = {Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use},

journal = {Nature Genetics},

year = {2019},

volume = {51},

publisher = {Springer Nature},

month = {jan},

url = {https://doi.org/10.1038/s41588-018-0307-5},

number = {2},

pages = {237--244},

doi = {10.1038/s41588-018-0307-5}

}

MLA

Cite this

MLA Copy

Liu, Mengzhen, et al. “Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.” Nature Genetics, vol. 51, no. 2, Jan. 2019, pp. 237-244. https://doi.org/10.1038/s41588-018-0307-5.

Publisher

Springer Nature

Journal

Nature Genetics

scimago Q1

wos Q1

SJR

16.586

CiteScore

45.1

Impact factor

29.0

ISSN

10614036 (Print)

15461718 (Electronic)