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

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.

doi:10.1073/pnas.1611243113

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

Details

Request a copy Under indefinite embargo.
UNIL restricted access
State: Public
Version: Final published version

Serval ID

serval:BIB_33980587AC78

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

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

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

URN

urn:nbn:ch:serval-BIB_33980587AC784

OAI-PMH

oai:serval.unil.ch:BIB_33980587AC78

DOI

10.1073/pnas.1611243113

Pubmed

27911795

Web of science

000389696700064

Open Access

Yes