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Record W2883645631 · doi:10.1038/s41467-018-05369-0

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

2018· review· en· W2883645631 on OpenAlexaff
Annah B. Wyss, Tamar Sofer, Mi Kyeong Lee, Natalie Terzikhan, Jennifer Nguyen, Lies Lahousse, Jeanne C. Latourelle, Albert V. Smith, Traci M. Bartz, Mary F. Feitosa, Wei Gao, Tarunveer S. Ahluwalia, Wenbo Tang, Christopher Oldmeadow, Qing Duan, Kim de Jong, Mary K. Wojczynski, Xin‐Qun Wang, Raymond Noordam, Fernando Pires Hartwig, Victoria E. Jackson, Tianyuan Wang, Ma’en Obeidat, Brian D. Hobbs, Tianxiao Huan, Hongsheng Gui, Margaret M. Parker, Donglei Hu, Lauren S. Mogil, Gleb Kichaev, Jianping Jin, Mariaelisa Graff, Tamara B. Harris, Ravi Kalhan, Susan R. Heckbert, Lavinia Paternoster, Kristin M. Burkart, Yongmei Liu, James G. Wilson, Judith M. Vonk, Jason L. Sanders, R. Graham Barr, Renée de Mutsert, Ana Maria Baptista Menezes, Hieab H.H. Adams, Maarten van den Berge, Roby Joehanes, Albert M. Levin, Jennifer Liberto, Lenore J. Launer, Alanna C. Morrison, Colleen M. Sitlani, Juan C. Celedón, Stephen B. Kritchevsky, Rodney J. Scott, Kaare Christensen, Jerome I. Rotter, Tobias Bonten, Fernando C. Wehrmeister, Yohan Bossé, Shujie Xiao, Sam S. Oh, Nora Franceschini, Jennifer A. Brody, Robert C. Kaplan, Kurt Lohman, Mark McEvoy, Michael A. Province, Frits R. Rosendaal, Kent D. Taylor, David C. Nickle, L. Keoki Williams, Esteban G. Burchard, Don D. Sin, Vilmundur Guðnason, Kari E. North, Myriam Fornage, Bruce M. Psaty, Richard H. Myers, George O'connor, Torben Hansen, Cathy C. Laurie, Patricia A. Cassano, Joohon Sung, Woo Jin Kim, John Attia, Leslie A. Lange, H. Marike Boezen, Bharat Thyagarajan, Stephen S. Rich, Dennis O. Mook‐Kanamori, Bernardo Lessa Horta, André G. Uitterlinden, Hae Kyung Im, Michael H. Cho, Guy Brusselle, Sina A. Gharib, Josée Dupuis, Ani Manichaikul, Stephanie J. London

Bibliographic record

VenueNature Communications · 2018
Typereview
Languageen
FieldMedicine
TopicChronic Obstructive Pulmonary Disease (COPD) Research
Canadian institutionsInstitut universitaire de cardiologie et de pneumologie de QuébecUniversité LavalSt. Paul's HospitalUniversity of British Columbia
FundersNational Institute of Environmental Health SciencesNational Human Genome Research InstituteNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteNational Institute on AgingU.S. Department of Health and Human ServicesNational Institutes of HealthLundbeckfondenUniversity of LeicesterNational Institute of General Medical SciencesSteno Diabetes Center Copenhagen
KeywordsLinkage disequilibriumGeneticsBiology1000 Genomes ProjectGenome-wide association studyGenomeGenomicsGenePopulationGenetic associationHuman genomeComputational biologyHaplotypeEvolutionary biologyAlleleSingle-nucleotide polymorphismGenotypeMedicine

Abstract

fetched live from OpenAlex

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

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), Research integrity
Consensus categoriesResearch integrity
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.770
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.004
Bibliometrics0.0010.002
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0020.001
Research integrity0.0010.003
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 head0.240
GPT teacher head0.468
Teacher spread0.227 · 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; both teacher heads agree on what is shown here.

Study designNot applicable
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

Citations129
Published2018
Admission routes1
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicChronic Obstructive Pulmonary Disease (COPD) ResearchFrench-language works237,207