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

  • Author(s): Schumann, G
  • Liu, C
  • O'Reilly, P
  • Gao, H
  • Song, P
  • Xu, B
  • Ruggeri, B
  • Amin, N
  • Jia, T
  • Preis, S
  • Lepe, MS
  • Akira, S
  • Barbieri, C
  • Baumeister, S
  • Cauchi, S
  • Clarke, TK
  • Enroth, S
  • Fischer, K
  • Hällfors, J
  • Harris, SE
  • Hieber, S
  • Hofer, E
  • Hottenga, JJ
  • Johansson, Å
  • Joshi, PK
  • Kaartinen, N
  • Laitinen, J
  • Lemaitre, R
  • Loukola, A
  • Luan, J
  • Lyytikäinen, LP
  • 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, AC
  • 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
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167198/
No data is associated with this publication.
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.

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