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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 ; 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. ; 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 beta-Klotho (KLB) as a locus associated with alcohol ...

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