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Schumann, G.* ; Liu, C.* ; O'Reilly, P.F.* ; Gao, H.* ; Song, P.* ; Xu, B.* ; Ruggeri, B.* ; Amin, N.* ; Jia, T.* ; Preis, S.R.* ; Lepe, M.S.* ; 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, A.* ; 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.J.* ; Nelson, C.P.* ; Nettleton, J.A.* ; 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.* ; Gieger, C. ; Elliott, P.* ; 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.J.* ; Eriksson, J.G.* ; Esko, T.* ; Eulenburg, V.* ; Huth, C.

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

Proc. Natl. Acad. Sci. U.S.A. 113, 14372-14377 (2016)
Publ. Version/Full Text Research data DOI
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Alcohol Consumption ; Fgf21 ; Human ; Mouse Model ; β-klotho; Genome-wide Association; Consumption; Disease; Activation; Dependence; Sweet; Liver; Heart; Mice
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 113, Issue: 50, Pages: 14372-14377 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Publishing Place Washington
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)