Schumann, G;
Liu, C;
O'Reilly, P;
Gao, H;
Song, P;
Xu, B;
Ruggeri, B;
... Elliott, P; + view all
(2016)
KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference.
Proceedings of the National Academy of Sciences of the United States of America
, 113
(50)
pp. 14372-14377.
10.1073/pnas.1611243113.
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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.
| Type: | Article |
|---|---|
| Title: | KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1073/pnas.1611243113 |
| Publisher version: | http://dx.doi.org/10.1073/pnas.1611243113 |
| Language: | English |
| Additional information: | Copyright © 2016 National Academy of Sciences. This is the accepted manuscript version of this article; the final published version can be found on the PNAS website at http://www.pnas.org/content/113/50/14372 |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, alcohol consumption, human, beta-Klotho, FGF21, mouse model, Genome-wide Association, Consumption, Disease, Activation, Dependence, Sweet, Liver, Heart, Mice |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1533255 |
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