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Record W3112768575 · doi:10.1101/2020.12.03.20242776

Genome-wide analysis of 944,133 individuals provides insights into the etiology of hemorrhoidal disease

2020· preprint· en· W3112768575 on OpenAlexaff
Tenghao Zheng, David Ellinghaus, Simonas Juzėnas, François Cossais, Greta Burmeister, Gabriele Mayr, Isabella Friis Jørgensen, Maris Teder‐Laving, Anne Heidi Skogholt, Karina Banasik, Thomas Becker, Frank Bokelmann, Søren Brunak, Stephan Buch, Hartmut Clausnizer, Christian Datz, Frauke Degenhardt, Marek J. Doniec, Christian Erikstrup, Tõnu Esko, Michael Förster, Norbert Frey, Lars G. Fritsche, Maiken E. Gabrielsen, Tobias Gräßle, Andrea Gsur, Justus Groß, Jochen Hampe, Alexander Hendricks, Sebastian Hinz, Kristian Hveem, Johannes Jongen, Ralf Junker, Tom H. Karlsen, Georg Hemmrich‐Stanisak, Wolfgang Kruis, Juozas Kupčinskas, Tilman Laubert, Matthias Laudes, Fabian H. Leendertz, Wolfgang Lieb, Verena Limperger, Nikolaos Margetis, Kerstin Mätz‐Rensing, Christopher Georg Németh, Eivind Ness‐Jensen, Ulrike Nowak‐Göttl, Anita Pandit, Ole Birger Pedersen, H.-G. Peleikis, Kenneth Peuker, Cristina Leal Rodríguez, Malte Rühlemann, Bodo Schniewind, Martin Schulzky, Jurgita Skiecevičienė, Jürgen Tepel, Laurent F. Thomas, Florian Uellendahl-Werth, Henrik Ullum, Ilka Vogel, Henry Völzke, Lorenzo von Fersen, Witigo von Schoenfels, Brett Vanderwerff, Julia Wilking, Michael Wittig, Sebastian Zeißig, Myrko Zobel, Matthew Zawistowski, Vladimir Vacic, Olga V. Sazonova, Elizabeth S. Noblin, Thilo Wedel, Volker Kahlke, Clemens Schafmayer, Mauro D’Amato, André Franke

Bibliographic record

VenuemedRxiv · 2020
Typepreprint
Languageen
FieldMedicine
TopicAnorectal Disease Treatments and Outcomes
Canadian institutionsInstitute of Cancer Research
FundersNovo Nordisk FondenNovo NordiskAustrian Science FundEuropean Regional Development FundHorizon 2020 Framework ProgrammeDeutsche ForschungsgemeinschaftVetenskapsrådetEesti TeadusagentuurTartu ÜlikoolDeutsches Zentrum für Herz-Kreislaufforschung
KeywordsEtiologyGenome-wide association studyHeritabilityBiologyDiseaseTranscriptomeExtracellular matrixPopulationGenetic architectureGeneticsGenetic associationGenetic predispositionBioinformaticsGenePathologyQuantitative trait locusMedicineGene expressionSingle-nucleotide polymorphismGenotype

Abstract

fetched live from OpenAlex

Abstract Hemorrhoidal disease (HEM) affects a large fraction of the population but its etiology including suspected genetic predisposition is poorly understood. We conducted a GWAS meta-analysis of 218,920 HEM patients and 725,213 controls of European ancestry, demonstrating modest heritability and genetic correlation with several other diseases from the gastrointestinal, neuroaffective and cardiovascular domains. HEM polygenic risk scores validated in 180,435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harboring genes whose expression is enriched in blood vessels and gastrointestinal tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses of affected tissue from HEM patients highlighted HEM gene co-expression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organization of the extracellular matrix. We conclude HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.

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)0.002
metaresearch head score (Gemma)0.003
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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0010.003
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
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 head0.023
GPT teacher head0.289
Teacher spread0.265 · 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
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

Citations0
Published2020
Admission routes1
Has abstractyes

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