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SHR Neuro Cancer Cardio Lipid Metab Microb

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.
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. 2016; 113(50):14372-14377 Doi: 10.1073/pnas.1611243113 [OPEN ACCESS]
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Co-authors Med Uni Graz

Hofer Edith

Schmidt Helena

Schmidt Reinhold

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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^-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.

Find related publications in this database (using NLM MeSH Indexing)

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 -

Find related publications in this database (Keywords)

alcohol consumption

human

beta-Klotho

FGF21

mouse model

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