Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
30643251
TITLE
Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.
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.
DATE PUBLISHED
2019 Jan 14
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2018/04/01
accepted 2018/11/06
entrez 2019/01/16 06:00
pubmed 2019/01/16 06:00
medline 2019/01/16 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Liu M Liu Mengzhen M Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Jiang Y Jiang Yu Y Institute of Personalized Medicine, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Wedow R Wedow Robbee R Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO, USA.
Li Y Li Yue Y The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brazel DM Brazel David M DM Interdisciplinary Quantitative Biology Graduate Group, University of Colorado Boulder, Boulder, CO, USA.
Chen F Chen Fang F Institute of Personalized Medicine, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Datta G Datta Gargi G Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Davila-Velderrain J Davila-Velderrain Jose J The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
McGuire D McGuire Daniel D Institute of Personalized Medicine, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Tian C Tian Chao C 23andMe, Inc., Mountain View, CA, USA.
Zhan X Zhan Xiaowei X Center for the Genetics of Host Defense, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
23andMe Research Team
HUNT All-In Psychiatry
Choquet H Choquet Hélène H Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Docherty AR Docherty Anna R AR Department of Psychiatry and Human Genetics, University of Utah, Salt Lake City, UT, USA.
Faul JD Faul Jessica D JD Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
Foerster JR Foerster Johanna R JR Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Fritsche LG Fritsche Lars G LG Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Gabrielsen ME Gabrielsen Maiken Elvestad ME K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Gordon SD Gordon Scott D SD Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Haessler J Haessler Jeffrey J Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Hottenga JJ Hottenga Jouke-Jan JJ Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Huang H Huang Hongyan H Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Jang SK Jang Seon-Kyeong SK Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Jansen PR Jansen Philip R PR Department of Child and Adolescent Psychiatry, Erasmus MC Rotterdam, Rotterdam, the Netherlands.
Ling Y Ling Yueh Y Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, USA.
Mägi R Mägi Reedik R Estonian Genome Center, University of Tartu, Tartu, Estonia.
Matoba N Matoba Nana N Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama City, Japan.
McMahon G McMahon George G Department of Population Health Science, Bristol Medical School, Oakfield Grove, Bristol, UK.
Mulas A Mulas Antonella A Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato, Italy.
Orrù V Orrù Valeria V Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato, Italy.
Palviainen T Palviainen Teemu T Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Pandit A Pandit Anita A Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Reginsson GW Reginsson Gunnar W GW deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Skogholt AH Skogholt Anne Heidi AH K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Smith JA Smith Jennifer A JA Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
Taylor AE Taylor Amy E AE Department of Population Health Science, Bristol Medical School, Oakfield Grove, Bristol, UK.
Turman C Turman Constance C Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Willemsen G Willemsen Gonneke G Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Young H Young Hannah H Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Young KA Young Kendra A KA Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Zajac GJM Zajac Gregory J M GJM Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Zhao W Zhao Wei W Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
Zhou W Zhou Wei W Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Bjornsdottir G Bjornsdottir Gyda G deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Boardman JD Boardman Jason D JD Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO, USA.
Boehnke M Boehnke Michael M Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Chen C Chen Chu C Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Cucca F Cucca Francesco F Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato, Italy.
Davies GE Davies Gareth E GE Avera Institute for Human Genetics, Sioux Falls, SD, USA.
Eaton CB Eaton Charles B CB Department of Family Medicine and Community Health, Alpert Medical School, Brown University, Providence, RI, USA.
Ehringer MA Ehringer Marissa A MA Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Esko T Esko Tõnu T Estonian Genome Center, University of Tartu, Tartu, Estonia.
Fiorillo E Fiorillo Edoardo E Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato, Italy.
Gillespie NA Gillespie Nathan A NA Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Gudbjartsson DF Gudbjartsson Daniel F DF School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
Haller T Haller Toomas T Estonian Genome Center, University of Tartu, Tartu, Estonia.
Harris KM Harris Kathleen Mullan KM Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.
Hewitt JK Hewitt John K JK Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Hickie IB Hickie Ian B IB Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia.
Hokanson JE Hokanson John E JE Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Hopfer CJ Hopfer Christian J CJ Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Hunter DJ Hunter David J DJ Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Iacono WG Iacono William G WG Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Johnson EO Johnson Eric O EO Fellows Program, RTI International, Research Triangle Park, NC, USA.
Kamatani Y Kamatani Yoichiro Y Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama City, Japan.
Kardia SLR Kardia Sharon L R SLR Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
Keller MC Keller Matthew C MC Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Kellis M Kellis Manolis M The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Kooperberg C Kooperberg Charles C Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Kraft P Kraft Peter P Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Krauter KS Krauter Kenneth S KS Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, USA.
Laakso M Laakso Markku M Department of Medicine, Kuopio University Hospital, Kuopio, Finland.
Lind PA Lind Penelope A PA Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Loukola A Loukola Anu A Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Lutz SM Lutz Sharon M SM Department of Biostatistics and Bioinformatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Madden PAF Madden Pamela A F PAF Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.
Martin NG Martin Nicholas G NG Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
McGue M McGue Matt M Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
McQueen MB McQueen Matthew B MB Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Medland SE Medland Sarah E SE Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu, Tartu, Estonia.
Mohlke KL Mohlke Karen L KL Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nielsen JB Nielsen Jonas B JB Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
Okada Y Okada Yukinori Y Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
Peters U Peters Ulrike U Department of Epidemiology, University of Washington, Seattle, WA, USA.
Polderman TJC Polderman Tinca J C TJC Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Posthuma D Posthuma Danielle D Department of Clinical Genetics, VU Medical Centre Amsterdam, Amsterdam, the Netherlands.
Reiner AP Reiner Alexander P AP Department of Epidemiology, University of Washington, Seattle, WA, USA.
Rice JP Rice John P JP Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Rimm E Rimm Eric E Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Rose RJ Rose Richard J RJ Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
Runarsdottir V Runarsdottir Valgerdur V SAA-National Center of Addiction Medicine, Vogur Hospital, Reykjavik, Iceland.
Stallings MC Stallings Michael C MC Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Stančáková A Stančáková Alena A Department of Internal Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Stefansson H Stefansson Hreinn H deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Thai KK Thai Khanh K KK Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Tindle HA Tindle Hilary A HA Department of Medicine, Vanderbilt University, Nashville, TN, USA.
Tyrfingsson T Tyrfingsson Thorarinn T SAA-National Center of Addiction Medicine, Vogur Hospital, Reykjavik, Iceland.
Wall TL Wall Tamara L TL Department of Psychiatry, University of California, San Diego, San Diego, CA, USA.
Weir DR Weir David R DR Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
Weisner C Weisner Constance C Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Whitfield JB Whitfield John B JB Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Winsvold BS Winsvold Bendik Slagsvold BS FORMI and Department of Neurology, Oslo University Hospital, Oslo, Norway.
Yin J Yin Jie J Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Zuccolo L Zuccolo Luisa L MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Bierut LJ Bierut Laura J LJ Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Hveem K Hveem Kristian K Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
Lee JJ Lee James J JJ Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Munafò MR Munafò Marcus R MR UK Centre for Tobacco and Alcohol Studies, School of Psychological Science, University of Bristol, Bristol, UK.
Saccone NL Saccone Nancy L NL Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Willer CJ Willer Cristen J CJ Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
Cornelis MC Cornelis Marilyn C MC Department of Preventative Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
David SP David Sean P SP Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Hinds DA Hinds David A DA 23andMe, Inc., Mountain View, CA, USA.
Jorgenson E Jorgenson Eric E Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Kaprio J Kaprio Jaakko J Department of Public Health, University of Helsinki, Helsinki, Finland.
Stitzel JA Stitzel Jerry A JA Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Stefansson K Stefansson Kari K Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Thorgeirsson TE Thorgeirsson Thorgeir E TE deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Abecasis G Abecasis Gonçalo G Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Liu DJ Liu Dajiang J DJ Institute of Personalized Medicine, College of Medicine, Pennsylvania State University, Hershey, PA, USA. dajiang.liu@psu.edu.
Vrieze S Vrieze Scott S Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA. vrieze@umn.edu.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Agee Michelle M
Alipanahi Babak B
Auton Adam A
Bell Robert K RK
Bryc Katarzyna K
Elson Sarah L SL
Fontanillas Pierre P
Furlotte Nicholas A NA
Hinds David A DA
Hromatka Bethann S BS
Huber Karen E KE
Kleinman Aaron A
Litterman Nadia K NK
McIntyre Matthew H MH
Mountain Joanna L JL
Northover Carrie A M CAM
Sathirapongsasuti J Fah JF
Sazonova Olga V OV
Shelton Janie F JF
Shringarpure Suyash S
Tian Chao C
Tung Joyce Y JY
Vacic Vladimir V
Wilson Catherine H CH
Pitts Steven J SJ
Mitchell Amy A
Skogholt Anne Heidi AH
Winsvold Bendik S BS
Sivertsen Børge B
Stordal Eystein E
Morken Gunnar G
Kallestad Håvard H
Heuch Ingrid I
Zwart John-Anker JA
Fjukstad Katrine Kveli KK
Pedersen Linda M LM
Gabrielsen Maiken Elvestad ME
Johnsen Marianne Bakke MB
Skrove Marit M
Indredavik Marit Sæbø MS
Drange Ole Kristian OK
Bjerkeset Ottar O
Børte Sigrid S
Stensland Synne Øien
JOURNAL
VOLUME:
ISSUE:
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2019
MONTH: Jan
DAY: 14
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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