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Record W2252526781 · doi:10.1038/ncomms9442

Genetic sharing and heritability of paediatric age of onset autoimmune diseases

2015· article· en· W2252526781 on OpenAlexaff
Leslie A. Lange, Sihai Dave Zhao, Jin Li, Jonathan P. Bradfield, Maedeh Mohebnasab, Laura Steel, Julie Kobie, Debra Abrams, Frank Mentch, Joseph Glessner, Yiran Guo, Zhi Wei, John J. Connolly, Christopher J. Cardinale, Marina Bakay, Dong Li, Sólrún Melkorka Maggadóttir, Kelly Thomas, Haijun Qui, Rosetta Chiavacci, Cecilia E. Kim, Fengxiang Wang, James W. Snyder, Berit Flatø, Øystein Førre, Lee A. Denson, Susan D. Thompson, Mara L. Becker, Stephen L. Guthery, Anna Latiano, Elena Pérez, Elena S. Resnick, Caterina Strisciuglio, Annamaria Staiano, Erasmo Miele, Mark S. Silverberg, Benedicte A. Lie, Marilynn Punaro, Richard K. Russell, David C. Wilson, Marla C. Dubinsky, Dimitri Monos, Vito Annese, Jane Munro, Carol A. Wise, Helen Chapel, Charlotte Cunningham‐Rundles, Jordan S. Orange, Edward M. Behrens, Kathleen E. Sullivan, Subra Kugathasan, Anne M. Griffiths, Jack Satsangi, Struan F.A. Grant, Patrick Sleiman, Terri H. Finkel, Constantin Polychronakos, Robert N. Baldassano, Eline T. Luning Prak, Justine A. Ellis, Hongzhe Li, Brendan J. Keating, Håkon Håkonarson

Bibliographic record

VenueNature Communications · 2015
Typearticle
Languageen
FieldImmunology and Microbiology
TopicT-cell and B-cell Immunology
Canadian institutionsMcGill UniversityHospital for Sick ChildrenUniversity of TorontoSickKids FoundationMount Sinai Hospital
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Human Genome Research InstituteCrohn's and Colitis UK
KeywordsHeritabilitySNPGenome-wide association studyPopulationGeneticsBiologyMissing heritability problemAutoimmune diseaseDiseaseMedicineImmunologySingle-nucleotide polymorphismGenotypeInternal medicineGeneAntibody

Abstract

fetched live from OpenAlex

Autoimmune diseases (AIDs) are polygenic diseases affecting 7-10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP-h(2)). SNP-h(2) estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP-h(2) in T1D and JIA, but does not significantly contribute to the pairwise rG. Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations between autoimmune diseases previously reported in adult cohorts.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.561
Threshold uncertainty score0.436

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.001
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 head0.021
GPT teacher head0.265
Teacher spread0.244 · 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.

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

Citations80
Published2015
Admission routes1
Has abstractyes

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