KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference

Journal article


Publication Details

Author(s): Schumann G, Liu C, O'Reilly P, Gao H, Song P, Xu B, Ruggeri B, Amin N, Jia T, Preis S, Lepe MS, Akira S, Barbieri C, Baumeister S, Cauchi S, Clarke TK, Enroth S, Fischer K, Hallfors J, Harris SE, Hieber S, Hofer E, Hottenga JJ, Johansson A, Joshi P, Kaartinen N, Laitinen J, Lemaitre R, Loukola A, Luan J, Lyytikainen LP, Mangino M, Manichaikul A, Mbarek H, Milaneschi Y, Moayyeri A, Mukamal K, Nelson C, Nettleton J, Partinen E, Rawal R, Robino A, Rose L, Sala C, Satoh T, Schmidt R, Schrautz K, Scott R, Smith AV, Starr JM, Teumer A, Trompet S, Uitterlinden AG, Venturini C, Vergnaud AC, Verweij N, Vitart V, Vuckovic D, Wedenoja J, Yengo L, Yu B, Zhang W, Zhao JH, Boomsma DI, Chambers J, Chasman DI, Daniela T, De Geus E, Deary I, Eriksson JG, Esko T, Eulenburg V, Franco OH, Froguel P, Gieger C, Grabe HJ, Gudnason V, Gyllensten U, Harris TB, Hartikainen AL, Heath AC, Hocking L, Hofman A, Huth C, Jarvelin MR, Jukema JW, Kaprio J, Kooner JS, Kutalik Z, Lahti J, Langenberg C, Lehtimaki T, Liu Y, Madden PAF, Martin N, Morrison A, Penninx B, Pirastu N, Psaty B, Raitakari O, Ridker P, Rose R, Rotter JI, Samani NJ, Schmidt H, Spector TD, Stott D, Strachan D, Tzoulaki I, Van Der Harst P, Van Duijn CM, Marques-Vidal P, Vollenweider P, Wareham NJ, Whitfield JB, Wilson J, Wolffenbuttel B, Bakalkin G, Evangelou E, Liu Y, Rice KM, Desrivieres S, Kliewer SA, Mangelsdorf DJ, Müller CP, Levy D, Elliott P
Journal: Proceedings of the National Academy of Sciences of the United States of America
Publication year: 2016
Volume: 113
Journal issue: 50
Pages range: 14372-14377
ISSN: 0027-8424
eISSN: 1091-6490


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 ?-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10(-12)). ?-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 ?-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.



FAU Authors / FAU Editors

Eulenburg, Volker PD Dr.
Lehrstuhl für Biochemie und Molekulare Medizin
Hieber, Sabrina
Medizinische Fakultät
Müller, Christian P. Prof. Dr.
Professur für Suchtmedizin


External institutions with authors

Beth Israel Deaconess Medical Center (BIDMC)
Boston University
Brigham and Women's Hospital (BWH)
Ealing Hospital NHS Trust
Erasmus University Medical Center
Fimlab Laboratories
Finnish Institute of Occupational Health (FIOH) / Työterveyslaitos (TTL)
Framingham Heart Study
Harvard University
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU)
Helsingin yliopisto / University of Helsinki
Icelandic Heart Association (IHA)
Imperial College London / The Imperial College of Science, Technology and Medicine
Indiana University
Istituto di ricovero e cura a carattere scientifico (IRCCS)
King’s College London
Lausanne University Hospital / Centre hospitalier universitaire vaudois (CHUV)
Leiden University
Ministry of Education of the People's Republic of China
National Institute for Health and Welfare (THL)
National Institute for Health and Welfare (THL)
National Institute on Aging (NIA)
Osaka University
Ospedale San Raffaele (früher: Centro San Raffaele del Monte Tabor Foundation)
Oulu University Hospital
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
St George's, University of London (SGUL) / St George's Hospital Medical School
Università degli Studi di Trieste
Universitätsmedizin Greifswald / Universitätsklinikum Greifswald
University of Aberdeen
University of California Los Angeles (UCLA)
University of Cambridge
University of Edinburgh
University of Glasgow
University of Groningen / Rijksuniversiteit Groningen
University of Leicester
University of Lille Nord de France / Université Lille Nord de France / Université Lille II
University of Tartu
University of Texas Health Science Center at Houston (UTHealth)
University of Texas Southwestern Medical Center (UT Southwestern)
University of Turku / Turun yliopisto
University of Virginia (UVA)
University of Washington
Uppsala University
Vrije Universiteit Amsterdam (VU) / University Amsterdam
Wake Forest University
Washington University


How to cite

APA:
Schumann, G., Liu, C., O'Reilly, P., Gao, H., Song, P., Xu, B.,... Elliott, P. (2016). KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference. Proceedings of the National Academy of Sciences of the United States of America, 113(50), 14372-14377. https://dx.doi.org/10.1073/pnas.1611243113

MLA:
Schumann, Gunter, et al. "KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference." Proceedings of the National Academy of Sciences of the United States of America 113.50 (2016): 14372-14377.

BibTeX: 

Last updated on 2019-06-08 at 09:02