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

Schumann, Gunter, Liu, Chunyu, O'Reilly, Paul, Gao, He, Song, Parkyong, Xu, Bing, Ruggeri, Barbara, Amin, Najaf, Jia, Tianye, Preis, Sarah, Lepe, Marcelo Segura, Akira, Shizuo, Barbieri, Caterina, Baumeister, Sebastian, Cauchi, Stephane, Clarke, Toni-Kim, Enroth, Stefan, Fischer, Krista, Hallfors, Jenni, Harris, Sarah E., Hieber, Saskia, Hofer, Edith, Hottenga, Jouke-Jan, Johansson, Asa, Joshi, PeterK., Kaartinen, Niina, Laitinen, Jaana, Lemaitre, Rozenn, Loukola, Anu, Luan, Jian'an, Lyytikainen, 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, Andre 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, Tonu, 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, Lehtimaki, 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., Desrivieres, Sylvane, Kliewer, Steven A., Mangelsdorf, David J., Muller, Christian P., Levy, Daniel and Elliott, Paul (2016) KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference. Proceedings of the National Academy of Sciences, 113 50: 14372-14377. doi:10.1073/pnas.1611243113


Author Schumann, Gunter
Liu, Chunyu
O'Reilly, Paul
Gao, He
Song, Parkyong
Xu, Bing
Ruggeri, Barbara
Amin, Najaf
Jia, Tianye
Preis, Sarah
Lepe, Marcelo Segura
Akira, Shizuo
Barbieri, Caterina
Baumeister, Sebastian
Cauchi, Stephane
Clarke, Toni-Kim
Enroth, Stefan
Fischer, Krista
Hallfors, Jenni
Harris, Sarah E.
Hieber, Saskia
Hofer, Edith
Hottenga, Jouke-Jan
Johansson, Asa
Joshi, PeterK.
Kaartinen, Niina
Laitinen, Jaana
Lemaitre, Rozenn
Loukola, Anu
Luan, Jian'an
Lyytikainen, 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, Andre 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, Tonu
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
Lehtimaki, 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.
Desrivieres, Sylvane
Kliewer, Steven A.
Mangelsdorf, David J.
Muller, Christian P.
Levy, Daniel
Elliott, Paul
Title KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference
Formatted title
KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference
Journal name Proceedings of the National Academy of Sciences   Check publisher's open access policy
ISSN 1091-6490
0027-8424
Publication date 2016-12-13
Sub-type Article (original research)
DOI 10.1073/pnas.1611243113
Open Access Status Not yet assessed
Volume 113
Issue 50
Start page 14372
End page 14377
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Formatted 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.
Keyword Alcohol consumption
FGF21
Human
Mouse model
β-Klotho
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 5 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sat, 04 Mar 2017, 01:00:43 EST by Web Cron on behalf of Learning and Research Services (UQ Library)