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Record W2618122943 · doi:10.1038/ncomms15382

Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

2017· review· en· W2618122943 on OpenAlexaff
Lam C. Tsoi, Philip E. Stuart, Chao Tian, Jóhann E. Guðjónsson, Sayantan Das, Matthew Zawistowski, Eva Ellinghaus, Vinod Chandran, Nick Dand, Kristina Callis Duffin, Charlotta Enerbäck, Tõnu Esko, André Franke, Dafna D. Gladman, Per Hoffmann, Külli Kingo, Sulev Kõks, Gerald G. Krueger, Henry W. Lim, Andres Metspalu, Ulrich Mrowietz, Sören Mucha, Proton Rahman, André Reis, Trilokraj Tejasvi, Richard C. Trembath, John J. Voorhees, Stephan Weidinger, Michael Weichenthal, Xiaoquan Wen, Nicholas Eriksson, Hyun Min Kang, David A. Hinds, Rajan P. Nair, Gonçalo R. Abecasis

Bibliographic record

VenueNature Communications · 2017
Typereview
Languageen
FieldImmunology and Microbiology
TopicPsoriasis: Treatment and Pathogenesis
Canadian institutionsMemorial University of NewfoundlandToronto Western HospitalUniversity of Toronto
FundersNational Center for Research ResourcesEuropean Regional Development FundNational Institute of Arthritis and Musculoskeletal and Skin DiseasesMedical Research CouncilNational Institutes of HealthTartu ÜlikoolHeinz Nixdorf StiftungDeutsche ForschungsgemeinschaftExzellenzclusters EntzündungsforschungNational Research FoundationKing's College LondonPsoriasis AssociationNational Human Genome Research InstituteWellcome TrustNational Psoriasis FoundationHelene Morgan Babcock and Alfred Babcock Memorial Scholarship TrustA. Alfred Taubman Medical Research InstituteDermatology FoundationBundesministerium für Bildung und ForschungNational Institute for Health and Care ResearchArthritis National Research FoundationU.S. Department of Veterans AffairsFoundation for the National Institutes of Health
KeywordsPsoriasisGenome-wide association studyGenetic architectureHeritabilityGeneticsGenetic associationBiologyMeta-analysisComputational biologyMedicineQuantitative trait locusSingle-nucleotide polymorphismImmunologyGeneGenotypeInternal medicine

Abstract

fetched live from OpenAlex

Abstract Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFκB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8 + T-cells and CD4 + T-cells including T H 0, T H 1 and T H 17). The identified loci explain ∼28% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset ( p= 2 × 10 −89 ). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.

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)0.005
metaresearch head score (Gemma)0.007
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: Review · Consensus signal: Review
Teacher disagreement score0.005
Threshold uncertainty score0.024

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0050.007
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0030.005
Bibliometrics0.0030.003
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
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 head0.122
GPT teacher head0.378
Teacher spread0.256 · 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
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

Citations400
Published2017
Admission routes1
Has abstractyes

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