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

Publication ,  Journal Article
Schumann, G; Liu, C; O'Reilly, P; Gao, H; Song, P; Xu, B; Ruggeri, B; Amin, N; Jia, T; Preis, S; Segura Lepe, M; Akira, S; Barbieri, C ...
Published in: Proc Natl Acad Sci U S A
December 13, 2016

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

December 13, 2016

Volume

113

Issue

50

Start / End Page

14372 / 14377

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice, 129 Strain
  • Mice
  • Membrane Proteins
  • Male
  • Liver
  • Klotho Proteins
  • Humans
 

Citation

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Schumann, G., Liu, C., O’Reilly, P., Gao, H., Song, P., Xu, B., … Elliott, P. (2016). KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference. Proc Natl Acad Sci U S A, 113(50), 14372–14377. https://doi.org/10.1073/pnas.1611243113
Schumann, Gunter, Chunyu Liu, Paul O’Reilly, He Gao, Parkyong Song, Bing Xu, Barbara Ruggeri, et al. “KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.Proc Natl Acad Sci U S A 113, no. 50 (December 13, 2016): 14372–77. https://doi.org/10.1073/pnas.1611243113.
Schumann G, Liu C, O’Reilly P, Gao H, Song P, Xu B, et al. KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference. Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14372–7.
Schumann, Gunter, et al. “KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.Proc Natl Acad Sci U S A, vol. 113, no. 50, Dec. 2016, pp. 14372–77. Pubmed, doi:10.1073/pnas.1611243113.
Schumann G, Liu C, O’Reilly P, Gao H, Song P, Xu B, Ruggeri B, Amin N, Jia T, Preis S, Segura Lepe M, 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 Å, Joshi PK, Kaartinen N, Laitinen J, Lemaitre R, Loukola A, Luan J, 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 AV, 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, Jukema JW, 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, Rice KM, Desrivières S, Kliewer SA, Mangelsdorf DJ, Müller CP, Levy D, Elliott P. KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference. Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14372–14377.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

December 13, 2016

Volume

113

Issue

50

Start / End Page

14372 / 14377

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice, 129 Strain
  • Mice
  • Membrane Proteins
  • Male
  • Liver
  • Klotho Proteins
  • Humans