Research output: Contribution to journal › Article › peer-review
Gunter Schumann, Chunyu Liu, Paul O'Reilly, He Gao, Parkyong Song, Bing Xu, Barbara Ruggeri, Najaf Amin, Tianye Jia, Sarah Preis, Marcelo Segura Lepe, Shizuo Akira, Caterina Barbieri, Sebastian Baumeister, Stephane Cauchi, Toni-Kim Clarke, Stefan Enroth, Krista Fischer, Jenni Hällfors, Sarah E Harris & 107 more
Original language | English |
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Pages (from-to) | 14372-14377 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 113 |
Issue number | 50 |
Early online date | 28 Nov 2016 |
DOIs | |
Accepted/In press | 18 Oct 2016 |
E-pub ahead of print | 28 Nov 2016 |
Published | 13 Dec 2016 |
KLB is associated with_SCHUMANN_Publishedonline28November2016_GREEN AAM NC
KLB_is_associated_with_SCHUMANN_Publishedonline28November2016_GREEN_AAM_NC.pdf, 2.19 MB, application/pdf
Uploaded date:19 Dec 2017
Version:Accepted author manuscript
Accepted author manuscript
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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