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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 ... view all 127 authors View less authors (2016)
Publisher: National Academy of Sciences
Languages: English
Types: Article
Subjects: mouse model, β-Klotho, FGF21, alcohol consumption, human, Biological Sciences

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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  • NWO | Large-area smart pressure-s...
  • EC | ePerMed

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