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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 OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.403
Threshold uncertainty score0.535

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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