KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.
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.
Duke Scholars
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- Polymorphism, Single Nucleotide
- Mice, Knockout
- Mice, Inbred C57BL
- Mice, 129 Strain
- Mice
- Membrane Proteins
- Male
- Liver
- Klotho Proteins
- Humans
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Polymorphism, Single Nucleotide
- Mice, Knockout
- Mice, Inbred C57BL
- Mice, 129 Strain
- Mice
- Membrane Proteins
- Male
- Liver
- Klotho Proteins
- Humans