Item type: | Article | ||||
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Journal or Publication Title: | Proceedings of the National Academy of Sciences | ||||
Publisher: | NATL ACAD SCIENCES | ||||
Place of Publication: | WASHINGTON | ||||
Volume: | 113 | ||||
Number of Issue or Book Chapter: | 50 | ||||
Page Range: | pp. 14372-14377 | ||||
Date: | 2016 | ||||
Institutions: | Medicine > Institut für Epidemiologie und Präventivmedizin | ||||
Identification Number: |
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Keywords: | GENOME-WIDE ASSOCIATION; CONSUMPTION; DISEASE; ACTIVATION; DEPENDENCE; SWEET; LIVER; HEART; MICE; alcohol consumption; human; beta-Klotho; FGF21; mouse model | ||||
Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
Status: | Published | ||||
Refereed: | Yes, this version has been refereed | ||||
Created at the University of Regensburg: | Yes | ||||
Item ID: | 42715 |
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 beta-Klotho (KLB) as a locus associated with alcohol ...
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 beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-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 beta-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.
Metadata last modified: 19 Feb 2021 05:50