Schumann, Gunter and Liu, Chunyu and O'Reilly, Paul and Gao, He and Song, Parkyong and Xu, Bing and Ruggeri, Barbara and Amin, Najaf and Jia, Tianye and Preis, Sarah and Lepe, Marcelo Segura and Akira, Shizuo and Barbieri, Caterina and Baumeister, Sebastian and Cauchi, Stephane and Clarke, Toni-Kim and Enroth, Stefan and Fischer, Krista and Hallfors, Jenni and Harris, Sarah E. and Hieber, Saskia and Hofer, Edith and Hottenga, Jouke-Jan and Johansson, Asa and Joshi, PeterK. and Kaartinen, Niina and Laitinen, Jaana and Lemaitre, Rozenn and Loukola, Anu and Luan, Jian'an and Lyytikainen, Leo-Pekka and Mangino, Massimo and Manichaikul, Ani and Mbarek, Hamdi and Milaneschi, Yuri and Moayyeri, Alireza and Mukamal, Kenneth and Nelson, Christopher and Nettleton, Jennifer and Partinen, Eemil and Rawal, Rajesh and Robino, Antonietta and Rose, Lynda and Sala, Cinzia and Satoh, Takashi and Schmidt, Reinhold and Schrautz, Katharina and Scott, Robert and Smith, Albert Vernon and Starr, John M. and Teumer, Alexander and Trompet, Stella and Uitterlinden, Andre G. and Venturini, Cristina and Vergnaud, Anne-Claire and Verweij, Niek and Vitart, Veronique and Vuckovic, Dragana and Wedenoja, Juho and Yengo, Loic and Yu, Bing and Zhang, Weihua and Zhao, Jing Hua and Boomsma, Dorret I. and Chambers, John and Chasman, Daniel I. and Daniela, Toniolo and de Geus, Eco and Deary, Ian and Eriksson, Johan G. and Esko, Tonu and Eulenburg, Volker and Franco, Oscar H. and Froguel, Philippe and Gieger, Christian and Grabe, Hans J. and Gudnason, Vilmundur and Gyllensten, Ulf and Harris, Tamara B. and Hartikainen, Anna-Liisa and Heath, Andrew C. and Hocking, Lynne and Hofman, Albert and Huth, Cornelia and Jarvelin, Marjo-Riitta and Jukema, J. Wouter and Kaprio, Jaakko and Kooner, Jaspal S. and Kutalik, Zoltan and Lahti, Jari and Langenberg, Claudia and Lehtimaki, Terho and Liu, Yongmei and Madden, Pamela A. F. and Martin, Nicholas and Morrison, Alanna and Penninx, Brenda and Pirastu, Nicola and Psaty, Bruce and Raitakari, Olli and Ridker, Paul and Rose, Richard and Rotter, Jerome I. and Samani, Nilesh J. and Schmidt, Helena and Spector, Tim D. and Stott, David and Strachan, David and Tzoulaki, Ioanna and van der Harst, Pim and van Duijn, Cornelia M. and Marques-Vidal, Pedro and Vollenweider, Peter and Wareham, Nicholas J. and Whitfield, John B. and Wilson, James and Wolffenbuttel, Bruce and Bakalkin, Georgy and Evangelou, Evangelos and Liu, Yun and Rice, Kenneth M. and Desrivieres, Sylvane and Kliewer, Steven A. and Mangelsdorf, David J. and Muller, Christian P. and Levy, Daniel and Elliott, Paul (2016) KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113 (50). pp. 14372-14377. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)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 beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-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 beta-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; CONSUMPTION; DISEASE; ACTIVATION; DEPENDENCE; SWEET; LIVER; HEART; MICE; alcohol consumption; human; beta-Klotho; FGF21; mouse model |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Apr 2019 13:24 |
| Last Modified: | 11 Apr 2019 13:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3788 |
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