KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference
-
Published:2016-11-28
Issue:50
Volume:113
Page:14372-14377
-
ISSN:0027-8424
-
Container-title:Proceedings of the National Academy of Sciences
-
language:en
-
Short-container-title:Proc Natl Acad Sci USA
Author:
Schumann Gunter, Liu Chunyu, O’Reilly Paul, Gao He, Song Parkyong, Xu Bing, Ruggeri Barbara, Amin Najaf, Jia Tianye, Preis Sarah, Segura Lepe Marcelo, Akira Shizuo, Barbieri Caterina, Baumeister Sebastian, Cauchi Stephane, Clarke Toni-Kim, Enroth Stefan, Fischer Krista, Hällfors Jenni, Harris Sarah E., Hieber Saskia, Hofer Edith, Hottenga Jouke-Jan, Johansson Åsa, Joshi Peter K., Kaartinen Niina, Laitinen Jaana, Lemaitre Rozenn, Loukola Anu, Luan Jian’an, Lyytikäinen Leo-Pekka, Mangino Massimo, Manichaikul Ani, Mbarek Hamdi, Milaneschi Yuri, Moayyeri Alireza, Mukamal Kenneth, Nelson Christopher, Nettleton Jennifer, Partinen Eemil, Rawal Rajesh, Robino Antonietta, Rose Lynda, Sala Cinzia, Satoh Takashi, Schmidt Reinhold, Schraut Katharina, Scott Robert, Smith Albert Vernon, Starr John M., Teumer Alexander, Trompet Stella, Uitterlinden André G., Venturini Cristina, Vergnaud Anne-Claire, Verweij Niek, Vitart Veronique, Vuckovic Dragana, Wedenoja Juho, Yengo Loic, Yu Bing, Zhang Weihua, Zhao Jing Hua, Boomsma Dorret I., Chambers John, Chasman Daniel I., Daniela Toniolo, de Geus Eco, Deary Ian, Eriksson Johan G., Esko Tõnu, Eulenburg Volker, Franco Oscar H., Froguel Philippe, Gieger Christian, Grabe Hans J., Gudnason Vilmundur, Gyllensten Ulf, Harris Tamara B., Hartikainen Anna-Liisa, Heath Andrew C., Hocking Lynne, Hofman Albert, Huth Cornelia, Jarvelin Marjo-Riitta, Jukema J. Wouter, Kaprio Jaakko, Kooner Jaspal S., Kutalik Zoltan, Lahti Jari, Langenberg Claudia, Lehtimäki Terho, Liu Yongmei, Madden Pamela A. F., Martin Nicholas, Morrison Alanna, Penninx Brenda, Pirastu Nicola, Psaty Bruce, Raitakari Olli, Ridker Paul, Rose Richard, Rotter Jerome I., Samani Nilesh J., Schmidt Helena, Spector Tim D., Stott David, Strachan David, Tzoulaki Ioanna, van der Harst Pim, van Duijn Cornelia M., Marques-Vidal Pedro, Vollenweider Peter, Wareham Nicholas J., Whitfield John B., Wilson James, Wolffenbuttel Bruce, Bakalkin Georgy, Evangelou Evangelos, Liu Yun, Rice Kenneth M., Desrivières Sylvane, Kliewer Steven A., Mangelsdorf David J.ORCID, Müller Christian P., Levy Daniel, Elliott Paul
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.
Publisher
Proceedings of the National Academy of Sciences
Subject
Multidisciplinary
Cited by
211 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|