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Record W4387358894 · doi:10.1101/2023.10.04.23296543

GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets

2023· preprint· en· W4387358894 on OpenAlexafffund
Nick Dand, Philip E. Stuart, John Bowes, David Ellinghaus, Joanne Nititham, Jake Saklatvala, Maris Teder‐Laving, Laurent F. Thomas, Tanel Traks, Steffen Uebe, G. Aßmann, David Baudry, Frank Behrens, Allison C. Billi, Matthew A. Brown, Harald Burkhardt, Francesca Capon, Raymond T. Chung, Charles Curtis, Michael Duckworth, Eva Ellinghaus, Oliver FitzGerald, Sascha Gerdes, C.E.M. Griffiths, Susanne Gulliver, Philip Helliwell, Pauline Ho, Per Hoffmann, Oddgeir L. Holmen, Zhiming Huang, Kristian Hveem, Deepak R. Jadon, Michaela Köhm, Cornelia Kraus, Céline Lamacchia, Sang Hyuck Lee, Feiyang Ma, Satveer K. Mahil, Neil McHugh, Ross McManus, Ellen Heilmann Modalsli, Michael J. Nissen, Markus M. Nöthen, Vinzenz Oji, Jorge R. Oksenberg, Matthew T. Patrick, Bethany E. Perez White, Andreas Ramming, Jürgen Rech, Cheryl F. Rosen, Mrinal K. Sarkar, Georg Schett, Börge Schmidt, Trilokraj Tejasvi, Heiko Traupe, John J. Voorhees, Eike Matthias Wacker, Richard B. Warren, Rachael Wasikowski, Stephan Weidinger, Xiaoquan Wen, Zhaolin Zhang, Anne Barton, Vinod Chandran, Tõnu Esko, John Foerster, André Franke, Dafna D. Gladman, Jóhann E. Guðjónsson, Wayne Gulliver, Ulrike Hüffmeier, Külli Kingo, Sulev Kõks, Wilson Liao, Mari Løset, Reedik Mägi, Rajan P. Nair, Proton Rahman, André Reis, Catherine Smith, Paola Di Meglio, Lam C. Tsoi, Michael A. Simpson, James T. Elder

Bibliographic record

VenuemedRxiv · 2023
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicPsoriasis: Treatment and Pathogenesis
Canadian institutionsToronto Western HospitalUniversity of TorontoMemorial University of NewfoundlandUniversity Health NetworkNexus Clinical Research (Canada)
FundersNorwegian Institute of Public HealthFaculty of Medicine and Health, University of SydneyMedical Research CouncilNIHR BioResourceManchester Biomedical Research CentreUniversity of California, San FranciscoMultiple Sclerosis Society of Western AustraliaNational Institutes of HealthHeinz Nixdorf StiftungVersus ArthritisSt. Olavs Hospital Universitetssykehuset i TrondheimNorges ForskningsrådKrembil FoundationInstitute of Psychiatry, Psychology and Neuroscience, King’s College LondonDeutsches Zentrum für Neurodegenerative ErkrankungenHelse Midt-NorgeDeutsche ForschungsgemeinschaftEuropean CommissionKing's College LondonU.S. Department of Veterans AffairsHelene Morgan Babcock and Alfred Babcock Memorial Scholarship TrustUniversity of TorontoEesti TeadusagentuurEuropean Federation of Pharmaceutical Industries and AssociationsNIHR Cambridge Biomedical Research CentreMaudsley CharityMultiple Sclerosis SocietyPfizerNational Psoriasis FoundationLEO FondetStiftelsen Kristian Gerhard JebsenNIHR Maudsley Biomedical Research CentreNorges Teknisk-Naturvitenskapelige UniversitetA. Alfred Taubman Medical Research InstituteFakultet for medisin og helsevitenskap, Norges Teknisk-Naturvitenskapelige UniversitetMichael J. Fox Foundation for Parkinson's ResearchEuropean Regional Development FundBundesministerium für Bildung und ForschungNational Institute for Health and Care Research
KeywordsPsoriasisGenome-wide association studyEpigeneticsBiologyDiseaseTranscriptomeGeneticsGenetic predispositionAlleleSingle-nucleotide polymorphismImmunologyMedicineGenotypeGeneGene expressionInternal medicine

Abstract

fetched live from OpenAlex

Abstract Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci. To move towards a saturation map of psoriasis susceptibility we meta-analysed 18 GWAS comprising 36,466 cases and 458,078 controls and identified 109 distinct psoriasis susceptibility loci, including 45 that have not been previously reported. These include susceptibility variants at loci in which the therapeutic targets IL17RA and AHR are encoded, and deleterious coding variants supporting potential new drug targets (including in STAP2 , CPVL and POU2F3 ). We conducted a transcriptome-wide association study to identify regulatory effects of psoriasis susceptibility variants and cross-referenced these against single cell expression profiles in psoriasis-affected skin, highlighting roles for the transcriptional regulation of haematopoietic cell development and epigenetic modulation of interferon signalling in psoriasis pathobiology.

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 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)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.183
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.095
GPT teacher head0.309
Teacher spread0.214 · 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 teacher head, not a consensus.

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

Citations31
Published2023
Admission routes2
Has abstractyes

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