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Record W314487992 · doi:10.1038/ncomms8001

Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci

2015· review· en· W314487992 on OpenAlexaff
Lam C. Tsoi, Sarah L. Spain, Eva Ellinghaus, Philip E. Stuart, Francesca Capon, Jo Knight, Trilokraj Tejasvi, Hyun Min Kang, Michael H. Allen, Sylviane Lambert, Stefan Stoll, Stephan Weidinger, Jóhann E. Guðjónsson, Sulev Kõks, Külli Kingo, Tõnu Esko, Sayantan Das, Andres Metspalu, Michael Weichenthal, Charlotta Enerbäck, Gerald G. Krueger, John J. Voorhees, Vinod Chandran, Cheryl F. Rosen, Proton Rahman, Dafna D. Gladman, André Reis, Rajan P. Nair, André Franke, Gonçalo R. Abecasis, Richard C. Trembath, James T. Elder

Bibliographic record

VenueNature Communications · 2015
Typereview
Languageen
FieldImmunology and Microbiology
TopicPsoriasis: Treatment and Pathogenesis
Canadian institutionsMemorial University of NewfoundlandToronto Western HospitalUniversity of TorontoCentre for Addiction and Mental Health
FundersEuropean Regional Development FundNational Institute of Arthritis and Musculoskeletal and Skin DiseasesMedical Research CouncilNational Institutes of HealthExzellenzclusters EntzündungsforschungTartu ÜlikoolDeutsche ForschungsgemeinschaftHeinz Nixdorf StiftungNational Institute for Health and Care ResearchBundesministerium für Bildung und ForschungU.S. Department of Veterans AffairsKing's College LondonPsoriasis AssociationWellcome Trust
KeywordsGenome-wide association studyBiologyGeneticsPsoriasisImputation (statistics)Genetic architectureGenetic associationComputational biologyDiseaseMeta-analysisHuman geneticsPopulationLocus (genetics)GenomeGenotypeEvolutionary biologyGeneQuantitative trait locusSingle-nucleotide polymorphismMedicineImmunology

Abstract

fetched live from OpenAlex

Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genome-wide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genome-wide significance (P<5 × 10−8). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3) and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2-dependent target of IL-17 signalling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies. About 2% of the population are affected by psoriasis, a chronic skin disease with complex genetics. Here Tsoi et al.conduct a meta-analysis of several genome-wide association studies and identify five novel loci, helping to further our understanding of the biology behind this condition.

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)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.649
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0040.002
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0020.001
Research integrity0.0020.001
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 head0.193
GPT teacher head0.435
Teacher spread0.243 · 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
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

Citations199
Published2015
Admission routes1
Has abstractyes

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