KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference

@article{Schumann2016KLBIA,
  title={KLB is associated with alcohol drinking, and its gene product $\beta$-Klotho is necessary for FGF21 regulation of alcohol preference},
  author={Gunter Schumann and Chunyu Liu and Paul F. O’Reilly and He Gao and Parkyong Song and Bing Xu and Barbara Ruggeri and Najaf Amin and Tianye Jia and Sarah Rosner Preis and Marcelo Segura Lepe and Shizuo Akira and Caterina M Barbieri and Sebastian E. Baumeister and St{\'e}phane Cauchi and Toni‐Kim Clarke and Stefan Enroth and Krista Fischer and Jenni H{\"a}llfors and Sarah E. Harris and Saskia Hieber and Edith Hofer and Jouke- Jan Hottenga and {\AA}sa Johansson and Peter K. Joshi and Niina E. Kaartinen and Jaana Laitinen and Rozenn N. Lemaitre and Anu Loukola and Jian’an Luan and Leo-Pekka Lyytik{\"a}inen and Massimo Mangino and Ani W. Manichaikul and Hamdi Mbarek and Yuri Milaneschi and Alireza Moayyeri and Kenneth J. Mukamal and Christopher P. Nelson and Jennifer A. Nettleton and Eemil Partinen and Rajesh Rawal and Antonietta Robino and Lynda M Rose and Cinzia Felicita Sala and Takashi Satoh and Reinhold Schmidt and Katharina E. Schraut and Robert A Scott and Albert Vernon Smith and John M. Starr and Alexander Teumer and Stella Trompet and Andr{\'e} G. Uitterlinden and Cristina Venturini and Anne-Claire Vergnaud and Niek Verweij and Veronique Vitart and Dragana Vuckovic and Juho Wedenoja and Loic Yengo and Bing Yu and Weihua Zhang and Jing Hua Zhao and Dorret I. Boomsma and John Campbell Chambers and Daniel I. Chasman and Toniolo Daniela and Eco J. C. de Geus and Ian J. Deary and Johan Gunnar Eriksson and T{\~o}nu Esko and Volker Eulenburg and Oscar H. Franco and Philippe Froguel and Christian Gieger and Hans J{\"o}rgen Grabe and Vilmundur G. Gudnason and Ulf Gyllensten and Tamara B. Harris and A-L. Hartikainen and Andrew C. Heath and Lynne J. Hocking and Albert Hofman and Cornelia Huth and Marjo-Riitta Jarvelin and J. Wouter Jukema and Jaakko A. Kaprio and Jaspal S Kooner and Zolt{\'a}n Kutalik and Jari Lahti and Claudia Langenberg and Terho Lehtim{\"a}ki and Yongmei Liu and Pamela A. F. Madden and Nicholas Martin and Alanna C. Morrison and Brenda W.J.H. Penninx and Nicola Pirastu and Bruce M. Psaty and Olli T. Raitakari and Paul M. Ridker and Richard J. Rose and Jerome I. Rotter and Nilesh J. Samani and Helena Schmidt and Tim D. Spector and David J. Stott and David P. Strachan and Ioanna Tzoulaki and Pim van der Harst and Cornelia M. van Duijn and Pedro Marques‐Vidal and Peter Vollenweider and Nicholas J. Wareham and John B. Whitfield and James F. Wilson and Bruce H. R. Wolffenbuttel and Georgy Bakalkin and Evangelos Evangelou and Yun Liu and Kenneth M. Rice and Sylvane Desrivi{\`e}res and Steven A. Kliewer and David J. Mangelsdorf and Christian P M{\"u}ller and Daniel Levy and Paul Elliott},
  journal={Proceedings of the National Academy of Sciences},
  year={2016},
  volume={113},
  pages={14372 - 14377}
}
Excessive alcohol consumption is a major public health problem worldwide. [...] Key Result 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.Expand
FGF21, a liver hormone that inhibits alcohol intake in mice, increases in human circulation after acute alcohol ingestion and sustained binge drinking at Oktoberfest
TLDR
FGF21 (1–181) is markedly increased in circulation by both acute and sub-chronic alcohol intake in humans, and reduces alcohol consumption in mice, consistent with a role for FGF21 as an endocrine inhibitor of alcohol appetite in humans. Expand
FGF21, a liver hormone that inhibits alcohol intake in mice, increases in human circulation after acute alcohol ingestion and sustained binge drinking at Oktoberfest
TLDR
FGF21 (1-181) is markedly increased in circulation by both acute and sub-chronic alcohol intake in humans, and reduces alcohol consumption in mice, consistent with a role for FGF21 as an endocrine inhibitor of alcohol appetite in humans. Expand
CUX2, BRAP and ALDH2 are associated with metabolic traits in people with excessive alcohol consumption
TLDR
The mechanism underlying the γ-GT-catalytic metabolic reaction in excessive alcohol consumption is associated with ALDH2, BRAP and CUX2 and the ridge coefficients of rs7398833, rs671 and rs3782886 were unchanged across different values of the shrinkage parameter. Expand
The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study
TLDR
The findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior. Expand
The Genetic Relationship Between Alcohol Consumption and Aspects of Problem Drinking in an Ascertained Sample.
TLDR
Genetic propensity for typical alcohol consumption was associated with alcohol use and was also associated with 4 of the additional 5 outcomes, though the variance explained in this sample was modest. Expand
Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank ( N = 112117 )
Alcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well-known genetic variants in alcohol metabolizing genes, for example, ALDH2 andExpand
Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)
TLDR
This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption. Expand
Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112,117)
TLDR
This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies 4 novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption. Expand
FGF21 Is a Sugar-Induced Hormone Associated with Sweet Intake and Preference in Humans.
TLDR
Data suggest the liver may secrete hormones that influence eating behavior and associations between FGF21 rs838133 and increased consumption of candy and nominal associations with increased alcohol intake and daily smoking are revealed. Expand
Genomewide Association Study of Alcohol Dependence and Related Traits in a Thai Population
TLDR
The first GWAS for 3 traits related to alcohol use in a Thai population recruited initially for studies of methamphetamine dependence showed genomewide significant association with variants near ALDH2, and significant pleiotropy between major depression and flushing was identified. Expand
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