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

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State: Public
Version: Final published version
Serval ID
serval:BIB_33980587AC78
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Schumann G., Liu C., O'Reilly P., Gao H., Song P., Xu B., Ruggeri B., Amin N., Jia T., Preis S., Segura Lepe M., Akira S., Barbieri C., Baumeister S., Cauchi S., Clarke T.K., Enroth S., Fischer K., Hällfors J., Harris S.E., Hieber S., Hofer E., Hottenga J.J., Johansson Å., Joshi P.K., Kaartinen N., Laitinen J., Lemaitre R., Loukola A., Luan J., Lyytikäinen L.P., 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., Schraut K., Scott R., Smith A.V., Starr J.M., Teumer A., Trompet S., Uitterlinden A.G., Venturini C., Vergnaud A.C., Verweij N., Vitart V., Vuckovic D., Wedenoja J., Yengo L., Yu B., Zhang W., Zhao J.H., Boomsma D.I., Chambers J., Chasman D.I., Daniela T., de Geus E., Deary I., Eriksson J.G., Esko T., Eulenburg V., Franco O.H., Froguel P., Gieger C., Grabe H.J., Gudnason V., Gyllensten U., Harris T.B., Hartikainen A.L., Heath A.C., Hocking L., Hofman A., Huth C., Jarvelin M.R., Jukema J.W., Kaprio J., Kooner J.S., Kutalik Z., Lahti J., Langenberg C., Lehtimäki T., Liu Y., Madden P.A., Martin N., Morrison A., Penninx B., Pirastu N., Psaty B., Raitakari O., Ridker P., Rose R., Rotter J.I., Samani N.J., Schmidt H., Spector T.D., Stott D., Strachan D., Tzoulaki I., van der Harst P., van Duijn C.M., Marques-Vidal P., Vollenweider P., Wareham N.J., Whitfield J.B., Wilson J., Wolffenbuttel B., Bakalkin G., Evangelou E., Liu Y., Rice K.M., Desrivières S., Kliewer S.A., Mangelsdorf D.J., Müller C.P., Levy D., Elliott P.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
13/12/2016
Peer-reviewed
Oui
Volume
113
Number
50
Pages
14372-14377
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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 β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10 javax.xml.bind.JAXBElement@78066a2c ). 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.

Keywords
Alcohol Drinking/genetics, Alcohol Drinking/physiopathology, Animals, Behavior, Animal/physiology, Brain/physiopathology, Emotions/physiology, Female, Fibroblast Growth Factors/physiology, Genome-Wide Association Study, Humans, Liver/physiopathology, Male, Membrane Proteins/deficiency, Membrane Proteins/genetics, Membrane Proteins/physiology, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Polymorphism, Single Nucleotide, FGF21, alcohol consumption, human, mouse model, β-Klotho
Pubmed
Web of science
Open Access
Yes
Create date
08/12/2016 17:37
Last modification date
20/08/2019 14:19
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