Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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
27911795
TITLE
KLB is associated with alcohol drinking, and its gene product ß-Klotho is necessary for FGF21 regulation of alcohol preference.
ABSTRACT
NlmCategory: UNASSIGNED
Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10(-12)). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
DATE PUBLISHED
2016 Dec 13
HISTORY
PUBSTATUS PUBSTATUSDATE
pmc-release 2017/06/13
pubmed 2016/12/03 06:00
medline 2016/12/03 06:00
entrez 2016/12/03 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Schumann G Schumann Gunter G Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom; gunter.schumann@kcl.ac.uk davo.mango@utsouthwestern.edu p.elliott@imperial.ac.uk.
Liu C Liu Chunyu C Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118.
O'Reilly P O'Reilly Paul P Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom.
Gao H Gao He H Medical Research Council-Public Health England Centre for Environment and Health, Imperial College London, London W2 1PG, United Kingdom.
Song P Song Parkyong P Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Xu B Xu Bing B Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom.
Ruggeri B Ruggeri Barbara B Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom.
Amin N Amin Najaf N Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
Jia T Jia Tianye T Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom.
Preis S Preis Sarah S Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118.
Segura Lepe M Segura Lepe Marcelo M Section of Bioinformatics, Bayer Pharma AG, 13342 Berlin, Germany.
Akira S Akira Shizuo S Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Barbieri C Barbieri Caterina C Division of Genetics and Cell Biology, San Raffaele Research Institute, 20132 Milan, Italy.
Baumeister S Baumeister Sebastian S Department of Epidemiology and Preventive Medicine, University of Regensburg, 93053 Regensburg, Germany.
Cauchi S Cauchi Stephane S CNRS UMR 8199, Lille Pasteur Institute, European Genomic Institute for Diabetes, Lille 2 University, 59000 Lille, France.
Clarke TK Clarke Toni-Kim TK Divison of Psychiatry, University of Edinburgh, Edinburgh EH10 5HF, United Kingdom.
Enroth S Enroth Stefan S Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, 75108 Uppsala, Sweden.
Fischer K Fischer Krista K Estonian Genome Center, University of Tartu, 51010 Tartu, Estonia.
Hällfors J Hällfors Jenni J Institute for Molecular Medicine, University of Helsinki, 00290 Helsinki, Finland.
Harris SE Harris Sarah E SE Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom.
Hieber S Hieber Saskia S Department of Psychiatry and Psychotherapy, Friedrich Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
Hofer E Hofer Edith E Institute of Medical Informatics, Statistics and Documentation, Medical University Graz, 8036 Graz, Austria.
Hottenga JJ Hottenga Jouke-Jan JJ Department of Biological Psychology, Vrije Universiteit Amsterdam and EMGO Institute for Health and Care Research, 1081 BT Amsterdam, The Netherlands.
Johansson Å Johansson Åsa Å Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, 75108 Uppsala, Sweden.
Joshi PK Joshi Peter K PK Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, United Kingdom.
Kaartinen N Kaartinen Niina N National Institute for Health and Welfare, 00271 Helsinki, Finland.
Laitinen J Laitinen Jaana J Quantified Employee-Unit, Finnish Institute of Occupational Health, 00250 Helsinki, Finland.
Lemaitre R Lemaitre Rozenn R Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101.
Loukola A Loukola Anu A Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.
Luan J Luan Jian'an J Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, United Kingdom.
Lyytikäinen LP Lyytikäinen Leo-Pekka LP Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere School of Medicine, Tampere 33520, Finland.
Mangino M Mangino Massimo M National Institute for Health Research Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London SE1 9RT, United Kingdom.
Manichaikul A Manichaikul Ani A Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22903.
Mbarek H Mbarek Hamdi H Department of Biological Psychology, Vrije Universiteit Amsterdam and EMGO Institute for Health and Care Research, 1081 BT Amsterdam, The Netherlands.
Milaneschi Y Milaneschi Yuri Y Department of Psychiatry, Institute for Health and Care Research (EMGO) Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam University Medical Center/Geestelijke Gezondheids Zorg (GGZ) inGeest, 1081 HL Amsterdam, The Netherlands.
Moayyeri A Moayyeri Alireza A Farr Institute of Health Informatics Research, University College London Institute of Health Informatics, London NW1 2DA, United Kingdom.
Mukamal K Mukamal Kenneth K Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
Nelson C Nelson Christopher C National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, United Kingdom.
Nettleton J Nettleton Jennifer J Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Sciences Center, Houston, TX 77225.
Partinen E Partinen Eemil E Faculty of Medicine, University of Tartu, 50411 Tartu, Estonia.
Rawal R Rawal Rajesh R Department of Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Robino A Robino Antonietta A Institute for Maternal and Child Health-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo, 34137 Trieste, Italy.
Rose L Rose Lynda L Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215.
Sala C Sala Cinzia C Division of Genetics and Cell Biology, San Raffaele Research Institute, 20132 Milan, Italy.
Satoh T Satoh Takashi T Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Schmidt R Schmidt Reinhold R Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz, 8036 Graz, Austria.
Schraut K Schraut Katharina K Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, United Kingdom.
Scott R Scott Robert R Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, United Kingdom.
Smith AV Smith Albert Vernon AV Research Institute, Icelandic Heart Association, 201 Kopavogur, Iceland.
Starr JM Starr John M JM Alzheimer Scotland Research Centre, University of Edinburgh, Edinburgh EH8 9JZ, United Kingdom.
Teumer A Teumer Alexander A Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany.
Trompet S Trompet Stella S Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Uitterlinden AG Uitterlinden André G AG Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
Venturini C Venturini Cristina C Department of Twin Research and Genetic Epidemiology, King's College, London SE1 7EH, United Kingdom.
Vergnaud AC Vergnaud Anne-Claire AC Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, United Kingdom.
Verweij N Verweij Niek N Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands.
Vitart V Vitart Veronique V Medical Research Council Human Genetics Unit, Institute for Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom.
Vuckovic D Vuckovic Dragana D Department of Medical Sciences, University of Trieste, 34149 Trieste, Italy.
Wedenoja J Wedenoja Juho J Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.
Yengo L Yengo Loic L CNRS UMR 8199, Lille Pasteur Institute, European Genomic Institute for Diabetes, Lille 2 University, 59000 Lille, France.
Yu B Yu Bing B Division of Epidemiology, University of Texas Health Science Center at Houston, Houston, TX 77225.
Zhang W Zhang Weihua W Department of Cardiology, Ealing Hospital, Middlesex UB1 3HW, United Kingdom.
Zhao JH Zhao Jing Hua JH Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, United Kingdom.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology, Vrije Universiteit Amsterdam and EMGO Institute for Health and Care Research, 1081 BT Amsterdam, The Netherlands.
Chambers J Chambers John J Imperial College Healthcare National Health Service Trust, London W12 0HS, United Kingdom.
Chasman DI Chasman Daniel I DI Harvard Medical School, Boston, MA 02115.
Daniela T Daniela Toniolo T Division of Genetics and Cell Biology, San Raffaele Research Institute, 20132 Milan, Italy.
de Geus E de Geus Eco E Department of Biological Psychology, Vrije Universiteit Amsterdam and EMGO Institute for Health and Care Research, 1081 BT Amsterdam, The Netherlands.
Deary I Deary Ian I Psychology, University of Edinburgh, Edinburgh EH8 9JZ, United Kingdom.
Eriksson JG Eriksson Johan G JG Vasa Central Hospital, 65130 Vasa, Finland.
Esko T Esko Tõnu T Estonian Genome Center, University of Tartu, 51010 Tartu, Estonia.
Eulenburg V Eulenburg Volker V Institute for Biochemistry and Molecular Medicine, Friedrich Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
Franco OH Franco Oscar H OH Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
Froguel P Froguel Philippe P Department of Genomics of Common Disease, School of Public Health, Imperial College London, London W12 0HR, United Kingdom.
Gieger C Gieger Christian C Department of Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Grabe HJ Grabe Hans J HJ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany.
Gudnason V Gudnason Vilmundur V Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
Gyllensten U Gyllensten Ulf U Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, 75108 Uppsala, Sweden.
Harris TB Harris Tamara B TB National Institute on Aging, NIH, Bethesda, MD 20892.
Hartikainen AL Hartikainen Anna-Liisa AL Unit of Primary Care, Oulu University Hospital, 90220 Oulu, Finland.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Hocking L Hocking Lynne L Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
Hofman A Hofman Albert A Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
Huth C Huth Cornelia C Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, D-85764 Neuherberg, Germany.
Jarvelin MR Jarvelin Marjo-Riitta MR Biocenter Oulu, University of Oulu, Oulu FI-90014, Finland.
Jukema JW Jukema J Wouter JW Department of Cardiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Kaprio J Kaprio Jaakko J Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.
Kooner JS Kooner Jaspal S JS Faculty of Medicine, National Heart & Lung Institute, Cardiovascular Science, Hammersmith Hospital, Imperial College London, London W12 0NN, United Kingdom.
Kutalik Z Kutalik Zoltan Z Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudoise, 1010 Lausanne, Switzerland.
Lahti J Lahti Jari J Institute of Behavioural Sciences, University of Helsinki, 00014 Helsinki, Finland.
Langenberg C Langenberg Claudia C Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, United Kingdom.
Lehtimäki T Lehtimäki Terho T Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere School of Medicine, Tampere 33520, Finland.
Liu Y Liu Yongmei Y Wake Forest School of Medicine, Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157.
Madden PA Madden Pamela A F PA Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
Martin N Martin Nicholas N Genetic Epidemiology, Queensland Institute of Medical Research Berghofer Medical Research Institute, Herston, Brisbane QLD 4029, Australia.
Morrison A Morrison Alanna A Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77225.
Penninx B Penninx Brenda B Department of Psychiatry, Institute for Health and Care Research (EMGO) Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam University Medical Center/Geestelijke Gezondheids Zorg (GGZ) inGeest, 1081 HL Amsterdam, The Netherlands.
Pirastu N Pirastu Nicola N Department of Medical Sciences, University of Trieste, 34149 Trieste, Italy.
Psaty B Psaty Bruce B Group Health Cooperative, Group Health Research Institute, Seattle, WA 98101.
Raitakari O Raitakari Olli O Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland.
Ridker P Ridker Paul P Harvard Medical School, Boston, MA 02115.
Rose R Rose Richard R Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405.
Rotter JI Rotter Jerome I JI Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA 90509.
Samani NJ Samani Nilesh J NJ National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, United Kingdom.
Schmidt H Schmidt Helena H Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, 8010 Graz, Austria.
Spector TD Spector Tim D TD Department of Twin Research and Genetic Epidemiology, King's College, London SE1 7EH, United Kingdom.
Stott D Stott David D Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow G31 2ER, United Kingdom.
Strachan D Strachan David D Population Health Research Institute, St. George's, University of London, London SW17 0RE, United Kingdom.
Tzoulaki I Tzoulaki Ioanna I Department of Hygiene and Epidemiology, University of Ioannina Medical School, 45110 Ioannina, Greece.
van der Harst P van der Harst Pim P Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute of The Netherlands-Netherlands Heart Institute, 3511GC Utrecht, The Netherlands.
van Duijn CM van Duijn Cornelia M CM Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
Marques-Vidal P Marques-Vidal Pedro P Department of Medicine, Internal Medicine, Lausanne University Hospital, 1011 Lausanne, Switzerland.
Vollenweider P Vollenweider Peter P Department of Medicine, Internal Medicine, Lausanne University Hospital, 1011 Lausanne, Switzerland.
Wareham NJ Wareham Nicholas J NJ Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, United Kingdom.
Whitfield JB Whitfield John B JB Genetic Epidemiology, Queensland Institute of Medical Research Berghofer Medical Research Institute, Herston, Brisbane QLD 4029, Australia.
Wilson J Wilson James J Medical Research Council Human Genetics Unit, Institute for Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom.
Wolffenbuttel B Wolffenbuttel Bruce B Department of Endocrinology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands.
Bakalkin G Bakalkin Georgy G Division of Biological Research on Drug Dependence, Department of Pharmaceutical, Biosciences, Uppsala University, 751 24 Uppsala, Sweden.
Evangelou E Evangelou Evangelos E Department of Hygiene and Epidemiology, University of Ioannina Medical School, 45110 Ioannina, Greece.
Liu Y Liu Yun Y Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, 200032 Shanghai, People's Republic of China.
Rice KM Rice Kenneth M KM Department of Biostatistics, University of Washington, Seattle, WA 98195.
Desrivières S Desrivières Sylvane S Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom.
Kliewer SA Kliewer Steven A SA Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Mangelsdorf DJ Mangelsdorf David J DJ Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Müller CP Müller Christian P CP Department of Psychiatry and Psychotherapy, Friedrich Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
Levy D Levy Daniel D The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD 20824.
Elliott P Elliott Paul P Medical Research Council-Public Health England Centre for Environment and Health, Imperial College London, London W2 1PG, United Kingdom.
INVESTIGATORS
JOURNAL
VOLUME: 113
ISSUE: 50
TITLE: Proceedings of the National Academy of Sciences of the United States of America
ISOABBREVIATION: Proc. Natl. Acad. Sci. U.S.A.
YEAR: 2016
MONTH: Dec
DAY: 13
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1091-6490
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Proc Natl Acad Sci U S A
COUNTRY: United States
ISSNLINKING: 0027-8424
NLMUNIQUEID: 7505876
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
P30 DK063491 NIDDK NIH HHS United States
UL1 TR000124 NCATS NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
FGF21
alcohol consumption
human
mouse model
ß-Klotho
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
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