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Record W3211151734 · doi:10.1016/j.xcrm.2021.100437

Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease

2021· review· en· W3211151734 on OpenAlexafffund
Nooshin Ghodsian, Erik Abner, Connor A. Emdin, Émilie Gobeil, Nele Taba, Mary E. Haas, Nicolas Perrot, Hasanga D. Manikpurage, Éloi Gagnon, Jérôme Bourgault, Alexis St-Amand, Christian Couture, Yohan Bossé, Patrick Mathieu, Marie‐Claude Vohl, André Tchernof, Sébastien Thériault, Amit V. Khera, Tõnu Esko, Benoît J. Arsenault

Bibliographic record

VenueCell Reports Medicine · 2021
Typereview
Languageen
FieldMedicine
TopicLiver Disease Diagnosis and Treatment
Canadian institutionsUniversité LavalInstitut universitaire de cardiologie et de pneumologie de Québec
FundersHorizon 2020Fonds de Recherche du Québec - SantéNovartis Institutes for BioMedical ResearchMedtronicNational Institutes of HealthEesti TeadusagentuurIonis PharmaceuticalsColumbia UniversityEuropean Regional Development FundInternational Business Machines CorporationSilence TherapeuticsEuropean CommissionPfizer
KeywordsFatty liverGenome-wide association studyInsulin resistanceDiseaseGenetic architectureGenetic predispositionApolipoprotein EBiologyMeta-analysisBioinformaticsMedicineGeneticsGenotypeInternal medicineDiabetes mellitusGeneSingle-nucleotide polymorphismEndocrinologyQuantitative trait locus

Abstract

fetched live from OpenAlex

Non-alcoholic fatty liver disease (NAFLD) is a complex disease linked to several chronic diseases. We aimed at identifying genetic variants associated with NAFLD and evaluating their functional consequences. We performed a genome-wide meta-analysis of 4 cohorts of electronic health record-documented NAFLD in participants of European ancestry (8,434 cases and 770,180 controls). We identify 5 potential susceptibility loci for NAFLD (located at or near GCKR , TR1B1 , MAU2 / TM6SF2 , APOE , and PNPLA3 ). We also report a potentially causal effect of lower LPL expression in adipose tissue on NAFLD susceptibility and an effect of the FTO genotype on NAFLD. Positive genetic correlations between NAFLD and cardiometabolic diseases and risk factors such as body fat accumulation/distribution, lipoprotein-lipid levels, insulin resistance, and coronary artery disease and negative genetic correlations with parental lifespan, socio-economic status, and acetoacetate levels are observed. This large GWAS meta-analysis reveals insights into the genetic architecture of NAFLD.

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)0.004
metaresearch head score (Gemma)0.012
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.005
Threshold uncertainty score0.022

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.012
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0050.007
Bibliometrics0.0040.007
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.000

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 head0.065
GPT teacher head0.324
Teacher spread0.260 · 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 designMeta-analysis
Domainnot available
GenreEmpirical

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
Published2021
Admission routes2
Has abstractyes

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