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

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Title: KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference
Authors: 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, TK
Enroth, S
Fischer, K
Hällfors, J
Harris, SE
Hieber, S
Hofer, E
Hottenga, JJ
Johansson, Å
Joshi, PK
Kaartinen, N
Laitinen, J
Lemaitre, R
Loukola, A
Luan, J
Lyytikäinen, 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
Schraut, 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
Lehtimäki, T
Liu, Y
Madden, PA
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
Desrivières, S
Kliewer, SA
Mangelsdorf, DJ
Müller, CP
Levy, D
Elliott, P
Item Type: Journal Article
Abstract: Alcohol is a widely consumed drug in western societies that can lead to addiction. A small shift in consumption can have dramatic consequences on public health. We performed the largest genome-wide association metaanalysis and replication study to date (>105,000 individuals) and identified a genetic basis for alcohol consumption during nonaddictive drinking. We found that a locus in the gene encoding β-Klotho is associated with alcohol consumption. β-Klotho is an essential receptor component for the endocrine FGFs, FGF19 and FGF21. Using mouse models and pharmacologic administration of FGF21, we show that β-Klotho in the brain controls alcohol drinking. These findings reveal a mechanism regulating alcohol consumption in humans that may be pharmacologically tractable for reducing alcohol intake.
Issue Date: 28-Nov-2016
Date of Acceptance: 18-Oct-2016
URI: http://hdl.handle.net/10044/1/43194
DOI: http://dx.doi.org/10.1073/pnas.1611243113
ISSN: 1091-6490
Publisher: National Academy of Sciences
Start Page: 14372
End Page: 14377
Journal / Book Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 113
Issue: 50
Copyright Statement: © 2016 National Academy of Sciences
Sponsor/Funder: National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Funder's Grant Number: NF-SI-0611-10136
RDC01 79560
MR/L01632X/1
MR/L01341X/1
RTJ6219303-1
Keywords: FGF21
alcohol consumption
human
mouse model
β-Klotho
MD Multidisciplinary
Publication Status: Published
Conference Place: United States
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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