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Record W2559170486 · doi:10.1073/pnas.1611243113

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

2016· review· en· W2559170486 on OpenAlexaff
Günter Schumann, Chunyu Liu, Paul F. O’Reilly, He Gao, Parkyong Song, Bing Xu, Barbara Ruggeri, Najaf Amin, Tianye Jia, Sarah R. Preis, Marcelo Segura Lepe, Shizuo Akira, Caterina Barbieri, Sebastian E. Baumeister, Stéphane Cauchi, Toni‐Kim Clarke, Stefan Enroth, Krista Fischer, Jenni Hällfors, Sarah E. Harris, Saskia Hieber, Edith Hofer, Jouke‐Jan Hottenga, Åsa Johansson, Peter K. Joshi, Niina E. Kaartinen, Jaana Laitinen, Rozenn N. Lemaître, Anu Loukola, Jian’an Luan, Leo‐Pekka Lyytikäinen, Massimo Mangino, Ani Manichaikul, Hamdi Mbarek, Yuri Milaneschi, Alireza Moayyeri, Kenneth J. Mukamal, Christopher Nelson, Jennifer A. Nettleton, Eemil Partinen, Rajesh Rawal, Antonietta Robino, Lynda M. Rose, Cinzia Sala, Takashi Satoh, Reinhold Schmidt, Katharina E. Schraut, Robert Scott, Albert V. Smith, John M. Starr, Alexander Teumer, Stella Trompet, André G. Uitterlinden, Cristina Venturini, Anne‐Claire Vergnaud, Niek Verweij, Véronique Vitart, Dragana Vuckovic, Juho Wedenoja, Loïc Yengo, Bing Yu, Weihua Zhang, Jing Hua Zhao, Dorret I. Boomsma, John C. Chambers, Daniel I. Chasman, Daniela Toniolo, Eco J. C. de Geus, Ian J. Deary, Johan G. Eriksson, Tõnu Esko, Volker Eulenburg, Oscar H. Franco, Philippe Froguel, Christian Gieger, Hans J. Grabe, Vilmundur Guðnason, Ulf Gyllensten, Tamara B. Harris, Anna-Liisa Hartikainen, Andrew C. Heath, Lynne J. Hocking, Albert Hofman, Cornelia Huth, Marjo‐Riitta Järvelin, J. Wouter Jukema, Jaakko Kaprio, Jaspal S. Kooner, Zoltán Kutalik, Jari Lahti, Claudia Langenberg, Terho Lehtimäki, Ching‐Ti Liu, Pamela A. F. Madden, Nicholas G. Martin, Alanna C. Morrison, Brenda W.J.H. Penninx, Nicola Pirastu, Bruce M. Psaty, Olli T. Raitakari, Paul M. Ridker, Richard J. Rose, Jerome I. Rotter, Nilesh J. Samani, Helena Schmidt, Tim D. Spector, David J. Stott, David P. Strachan, Ioanna Tzoulaki, Pim van der Harst, Cornelia M. van Duijn, Pedro Marques‐Vidal, Péter Vollenweider, Nicholas J. Wareham, John B. Whitfield, James F. Wilson, Bruce H. R. Wolffenbuttel, Georgy Bakalkin, Εvangelos Εvangelou, Yun Liu, Kenneth Rice, Sylvane Desrivières, Steven A. Kliewer, David J. Mangelsdorf, Christian P. Müller, Daniel Levy, Paul Elliott

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2016
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicFibroblast Growth Factor Research
Canadian institutionsCentre for Global Health Research
FundersNational Center for Advancing Translational SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteNational Health and Medical Research CouncilMedical Research CouncilForskningsrådet om Hälsa, Arbetsliv och VälfärdFondation LeenaardsNational Cancer InstituteNational Institute on Alcohol Abuse and AlcoholismSvenska Forskningsrådet FormasNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungGlaxoSmithKlineDeutsche ForschungsgemeinschaftEuropean CommissionNational Institute for Health and Care ResearchBundesministerium für Bildung und ForschungNational Science Foundation
KeywordsFGF21KlothoAlcoholAlcohol consumptionBiologyMedicineGeneticsFibroblast growth factorReceptorBiochemistry

Abstract

fetched live from OpenAlex

Significance Alcohol is a widely consumed drug in western societies that can lead to addiction. A small shift in consumption can have dramatic consequences on public health. We performed the largest genome-wide association metaanalysis and replication study to date (&gt;105,000 individuals) and identified a genetic basis for alcohol consumption during nonaddictive drinking. We found that a locus in the gene encoding β-Klotho is associated with alcohol consumption. β-Klotho is an essential receptor component for the endocrine FGFs, FGF19 and FGF21. Using mouse models and pharmacologic administration of FGF21, we show that β-Klotho in the brain controls alcohol drinking. These findings reveal a mechanism regulating alcohol consumption in humans that may be pharmacologically tractable for reducing alcohol intake.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.113
GPT teacher head0.364
Teacher spread0.252 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations253
Published2016
Admission routes1
Has abstractyes

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