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KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.
Friday,2016-12-16 21:13 America/Los_Angeles — ecterry
| Title | KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Schumann, G, Liu, C, O'Reilly, P, Gao, H, Song, P, Xu, B, Ruggeri, B, Amin, N, Jia, T, Preis, S, Lepe, MSegura, Akira, S, Barbieri, C, Baumeister, S, Cauchi, S, Clarke, T-K, Enroth, S, Fischer, K, Hällfors, J, Harris, SE, Hieber, S, Hofer, E, Hottenga, J-J, Johansson, A, Joshi, PK, Kaartinen, N, Laitinen, J, Lemaitre, R, Loukola, A, Luan, J'an, Lyytikäinen, L-P, 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, AVernon, Starr, JM, Teumer, A, Trompet, S, Uitterlinden, AG, Venturini, C, Vergnaud, A-C, 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, A-L, Heath, AC, Hocking, L, Hofman, A, Huth, C, Jarvelin, M-R, J Jukema, W, Kaprio, J, Kooner, JS, Kutalik, Z, Lahti, J, Langenberg, C, Lehtimäki, T, Liu, Y, Madden, PAF, 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 |
| Journal | Proc Natl Acad Sci U S A |
| Volume | 113 |
| Issue | 50 |
| Pagination | 14372-14377 |
| Date Published | 2016 Dec 13 |
| ISSN | 1091-6490 |
| Abstract | <p>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.</p> |
| DOI | 10.1073/pnas.1611243113 |
| Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
| PubMed ID | 27911795 |
ePub date:
16/12