Your browser doesn't support javascript.
loading
KLB is associated with alcohol drinking, and its gene product ß-Klotho is necessary for FGF21 regulation of alcohol preference.
Schumann, Gunter; Liu, Chunyu; O'Reilly, Paul; Gao, He; Song, Parkyong; Xu, Bing; Ruggeri, Barbara; Amin, Najaf; Jia, Tianye; Preis, Sarah; Segura Lepe, Marcelo; Akira, Shizuo; Barbieri, Caterina; Baumeister, Sebastian; Cauchi, Stephane; Clarke, Toni-Kim; Enroth, Stefan; Fischer, Krista; Hällfors, Jenni; Harris, Sarah E; Hieber, Saskia; Hofer, Edith; Hottenga, Jouke-Jan; Johansson, Åsa; Joshi, Peter K; Kaartinen, Niina; Laitinen, Jaana; Lemaitre, Rozenn; Loukola, Anu; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Mangino, Massimo; Manichaikul, Ani; Mbarek, Hamdi; Milaneschi, Yuri; Moayyeri, Alireza; Mukamal, Kenneth; Nelson, Christopher; Nettleton, Jennifer; Partinen, Eemil; Rawal, Rajesh; Robino, Antonietta; Rose, Lynda; Sala, Cinzia; Satoh, Takashi; Schmidt, Reinhold; Schraut, Katharina; Scott, Robert; Smith, Albert Vernon; Starr, John M.
Affiliation
  • Schumann 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; The Framingham Heart Study, Framingham, MA 01702.
  • O'Reilly P; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD 20824.
  • Gao H; Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118.
  • Song P; Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom.
  • Xu B; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, United Kingdom.
  • Ruggeri B; Medical Research Council-Public Health England Centre for Environment and Health, Imperial College London, London W2 1PG, United Kingdom.
  • Amin N; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
  • Jia T; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390.
  • Preis S; Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom.
  • Segura Lepe M; Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom.
  • Akira S; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
  • Barbieri C; Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom.
  • Baumeister S; Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118.
  • Cauchi S; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, United Kingdom.
  • Clarke TK; Section of Bioinformatics, Bayer Pharma AG, 13342 Berlin, Germany.
  • Enroth S; Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
  • Fischer K; Division of Genetics and Cell Biology, San Raffaele Research Institute, 20132 Milan, Italy.
  • Hällfors J; Institute for Community Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
  • Harris SE; Department of Epidemiology and Preventive Medicine, University of Regensburg, 93053 Regensburg, Germany.
  • Hieber S; CNRS UMR 8199, Lille Pasteur Institute, European Genomic Institute for Diabetes, Lille 2 University, 59000 Lille, France.
  • Hofer E; Divison of Psychiatry, University of Edinburgh, Edinburgh EH10 5HF, United Kingdom.
  • Hottenga JJ; Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, 75108 Uppsala, Sweden.
  • Johansson Å; Estonian Genome Center, University of Tartu, 51010 Tartu, Estonia.
  • Joshi PK; Institute for Molecular Medicine, University of Helsinki, 00290 Helsinki, Finland.
  • Kaartinen N; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, United Kingdom.
  • Laitinen J; Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom.
  • Lemaitre R; Department of Psychiatry and Psychotherapy, Friedrich Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
  • Loukola A; Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz, 8036 Graz, Austria.
  • Luan J; Institute of Medical Informatics, Statistics and Documentation, Medical University Graz, 8036 Graz, Austria.
  • Lyytikäinen LP; Department of Biological Psychology, Vrije Universiteit Amsterdam and EMGO Institute for Health and Care Research, 1081 BT Amsterdam, The Netherlands.
  • Mangino M; Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, 75108 Uppsala, Sweden.
  • Manichaikul A; Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, United Kingdom.
  • Mbarek H; National Institute for Health and Welfare, 00271 Helsinki, Finland.
  • Milaneschi Y; Quantified Employee-Unit, Finnish Institute of Occupational Health, 00250 Helsinki, Finland.
  • Moayyeri A; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101.
  • Mukamal K; Institute for Molecular Medicine, University of Helsinki, 00290 Helsinki, Finland.
  • Nelson C; Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.
  • Nettleton J; Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, United Kingdom.
  • Partinen E; Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere School of Medicine, Tampere 33520, Finland.
  • Rawal R; Department of Twin Research and Genetic Epidemiology, King's College, London SE1 7EH, United Kingdom.
  • Robino A; National Institute for Health Research Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London SE1 9RT, United Kingdom.
  • Rose L; Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22903.
  • Sala C; Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22903.
  • Satoh T; Department of Biological Psychology, Vrije Universiteit Amsterdam and EMGO Institute for Health and Care Research, 1081 BT Amsterdam, The Netherlands.
  • Schmidt R; 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.
  • Schraut K; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, United Kingdom.
  • Scott R; Institute of Health Informatics, University College London, London NW1 2DA, United Kingdom.
  • Smith AV; Farr Institute of Health Informatics Research, University College London Institute of Health Informatics, London NW1 2DA, United Kingdom.
  • Starr JM; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
Proc Natl Acad Sci U S A ; 113(50): 14372-14377, 2016 12 13.
Article in En | MEDLINE | ID: mdl-27911795
ABSTRACT
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 ß-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10-12). ß-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 ß-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.
Subject(s)
Key words
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alcohol Drinking / Fibroblast Growth Factors / Membrane Proteins Type of study: Prognostic_studies / Risk_factors_studies / Systematic_reviews Aspects: Patient_preference Limits: Animals / Female / Humans / Male Language: En Journal: Proc Natl Acad Sci U S A Year: 2016 Document type: Article
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alcohol Drinking / Fibroblast Growth Factors / Membrane Proteins Type of study: Prognostic_studies / Risk_factors_studies / Systematic_reviews Aspects: Patient_preference Limits: Animals / Female / Humans / Male Language: En Journal: Proc Natl Acad Sci U S A Year: 2016 Document type: Article