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Record W2807796131 · doi:10.1101/343293

New genetic signals for lung function highlight pathways and pleiotropy, and chronic obstructive pulmonary disease associations across multiple ancestries

2018· preprint· en· W2807796131 on OpenAlexaff
Nick Shrine, Anna L. Guyatt, A. Mesut Erzurumluoglu, Victoria E. Jackson, Brian D. Hobbs, Carl Melbourne, Chiara Batini, Katherine A. Fawcett, Kijoung Song, Phuwanat Sakornsakolpat, Xingnan Li, Ruth Boxall, Nicola Reeve, Ma’en Obeidat, Jing Hua Zhao, Matthias Wielscher, Understanding Society Scientific Group, Stefan Weiß, Katherine A. Kentistou, James P. Cook, Benjamin B. Sun, Jian Zhou, Jennie Hui, Stefan Karrasch, Medea Imboden, Sarah E. Harris, Jonathan Marten, Stefan Enroth, Shona M. Kerr, Ida Surakka, Véronique Vitart, Terho Lehtimäki, Richard J. Allen, Per Bakke, Terri H. Beaty, Eugene R. Bleecker, Yohan Bossé, Corry‐Anke Brandsma, Zhengming Chen, James D. Crapo, John Danesh, Dawn L. DeMeo, Frank Dudbridge, Ralf Ewert, Christian Gieger, Amund Gulsvik, Anna Hansell, Ke Hao, Josh D Hoffman, John E. Hokanson, Georg Homuth, Peter K. Joshi, Philippe Joubert, Claudia Langenberg, Xuan Li, Liming Li, Kuang Lin, Lars Lind, Nick Locantore, Jian’an Luan, Anubha Mahajan, Joseph Maranville, Alison D. Murray, David C. Nickle, Richard Packer, Margaret M. Parker, Megan L. Paynton, David J. Porteous, Dmitry Prokopenko, Dandi Qiao, Rajesh Rawal, Heiko Runz, Ian Sayers, Don D. Sin, Blair H. Smith, María Soler Artigas, David Sparrow, Ruth Tal‐Singer, Paul R. H. J. Timmers, Maarten van den Berge, John C. Whittaker, Prescott G. Woodruff, Laura M Yerges Armstrong, Olga G. Troyanskaya, Olli T. Raitakari, Mika Kähönen, Ozren Polašek, Ulf Gyllensten, Igor Rudan, Ian J. Deary, Nicole Probst‐Hensch, Holger Schulz, James F. Wilson, Beate Stubbe, Eleftheria Zeggini, Marjo‐Riitta Järvelin, Edwin K. Silverman, Caroline Hayward, Andrew P. Morris, Adam S. Butterworth, Robert A. Scott, Robin Walters, Deborah A. Meyers, Michael H. Cho, David P. Strachan, Ian P. Hall, Martin D. Tobin, Louise V. Wain

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldMedicine
TopicChronic Obstructive Pulmonary Disease (COPD) Research
Canadian institutionsInstitut universitaire de cardiologie et de pneumologie de QuébecCentre for Global Health ResearchUniversité LavalSt. Paul's HospitalUniversity of British Columbia
FundersNIHR Nottingham Biomedical Research CentreNIHR Leicester Biomedical Research CentreNational Heart, Lung, and Blood InstituteNIHR Cambridge Biomedical Research CentreEconomic and Social Research CouncilMedical Research CouncilUppsala UniversitetHjärt-LungfondenCenters for Disease Control and PreventionMinistry of Science and Technology of the People's Republic of ChinaWellcome TrustUniversity of EssexCancer Research UKBHF Centre of Research Excellence, OxfordVetenskapsrådetNational Natural Science Foundation of ChinaUnderstanding SocietyEuropean CommissionBritish Lung FoundationBundesministerium für Bildung und ForschungNHS Blood and TransplantNational Institute for Health and Care ResearchHorizon 2020 Framework ProgrammeBritish Heart FoundationUniversity of CambridgeDeutsche ForschungsgemeinschaftGlaxoSmithKlineNational Institutes of HealthUniversity of Leicester
KeywordsPleiotropyCOPDPhenomeLung functionGenome-wide association studyDiseaseGenetic associationPulmonary diseaseLungGenetic variantsMedicineMultimorbidityBioinformaticsBiologyGenomeGeneticsPhenotypeInternal medicineGenotypeSingle-nucleotide polymorphismGene

Abstract

fetched live from OpenAlex

Abstract Reduced lung function predicts mortality and is key to the diagnosis of COPD. In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, one-half of which are new. In combination these variants strongly predict COPD in deeply-phenotyped patient populations. Furthermore, the combined effect of these variants showed generalisability across smokers and never-smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.

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)0.001
metaresearch head score (Gemma)0.002
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
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.001
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 head0.019
GPT teacher head0.263
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 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

Citations11
Published2018
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicChronic Obstructive Pulmonary Disease (COPD) Research→French-language works237,207→