Evidence map›Paper›PMID 36914875›Full record

SynthesisNature genetics2023

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Nick Shrine, Abril G Izquierdo, Jing Chen, Richard Packer, Robert J Hall, Anna L Guyatt, Chiara Batini, Rebecca J Thompson, Chandan Pavuluri, Vidhi Malik and 140 more

Erratum issuedOpen access · hybridFull text readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 122 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 10 pooled it
45.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

122 citing papers in PubMed, 10 syntheses or guidelines pooled it, 173 citations in OpenAlex.

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  12. Preclinical models of COPD: a state of the art review.The European respiratory journal · 2026
    Review
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62 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

150 authors at 20 institutions in 14 countries.

Nick Shrine *Department of Population Health Sciences, University of Leicester, Leicester, UK. nick.shrine@leicester.ac.uk.ORCID http://orcid.org/0000-0003-3641-4371
Abril G Izquierdo *Department of Population Health Sciences, University of Leicester, Leicester, UK.
Jing Chen *Department of Population Health Sciences, University of Leicester, Leicester, UK.ORCID http://orcid.org/0000-0003-1287-1930
Richard Packer *Department of Population Health Sciences, University of Leicester, Leicester, UK.
Robert J HallDivision of Respiratory Medicine and NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK.
Anna L GuyattDepartment of Population Health Sciences, University of Leicester, Leicester, UK.ORCID http://orcid.org/0000-0003-1860-6337
Chiara BatiniDepartment of Population Health Sciences, University of Leicester, Leicester, UK.
Rebecca J ThompsonDivision of Respiratory Medicine and NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK.
Chandan PavuluriChanning Division of Network Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Vidhi MalikChanning Division of Network Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Brian D HobbsChanning Division of Network Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9564-0745
Matthew MollChanning Division of Network Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Wonji KimChanning Division of Network Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1249-797X
Ruth Tal-SingerCOPD Foundation, Washington DC, USA.
Per BakkeDepartment of Clinical Science, Unversity of Bergen, Bergen, Norway.
Katherine A FawcettDepartment of Population Health Sciences, University of Leicester, Leicester, UK.
Catherine JohnDepartment of Population Health Sciences, University of Leicester, Leicester, UK.
Kayesha ColeyDepartment of Population Health Sciences, University of Leicester, Leicester, UK.ORCID http://orcid.org/0000-0003-4951-6799
Noemi Nicole PigaDepartment of Population Health Sciences, University of Leicester, Leicester, UK.
Alfred PozarickijNuffield Department of Population Health, University of Oxford, Oxford, UK.
Kuang LinNuffield Department of Population Health, University of Oxford, Oxford, UK.
Iona Y MillwoodNuffield Department of Population Health, University of Oxford, Oxford, UK.
Zhengming ChenNuffield Department of Population Health, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-6423-105X
Liming LiDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.ORCID http://orcid.org/0000-0001-5873-7089
China Kadoorie Biobank Collaborative Group
Sara R A WijnantDepartment of Respiratory Diseases, Ghent Universital Hospital, Ghent, Belgium.
Lies LahousseDepartment of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.ORCID http://orcid.org/0000-0002-3494-4363
Guy BrusselleDepartment of Respiratory Diseases, Ghent Universital Hospital, Ghent, Belgium.
Andre G UitterlindenDepartment of Internal Medicine, Eramus Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-7276-3387
Ani ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Elizabeth C OelsnerDepartment of Medicine, Columbia University Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-7481-9671
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0003-3872-7793
R Graham BarrDepartment of Medicine, Columbia University Medical Center, New York, NY, USA.
Shona M KerrMedical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-4137-1495
Veronique VitartMedical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-4991-3797
Michael R BrownHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Matthias WielscherMRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Medea ImbodenDepartment of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
Ayoung JeongDepartment of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Allschwil, Switzerland.ORCID http://orcid.org/0000-0003-1542-0756
Traci M BartzCardiovascular Health Research Unit, Departments of Medicine and Biostatistics, University of Washington, Seattle, WA, USA.
Sina A GharibComputational Medicine Core, Center for Lung Biology, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-2480-4367
Claudia FlexederInstitute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Munich, Germany.
Stefan KarraschInstitute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Munich, Germany.
Christian GiegerInstitute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0001-6986-9554
Annette PetersInstitute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0001-6645-0985
Beate StubbeDepartment of Internal Medicine B-Cardiology, Intensive Care, Pulmonary Medicine and Infectious Diseases, University Medicine Greifswald, Greifswald, Germany.
Xiaowei HuCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0001-7804-7392
Victor E OrtegaDivision of Respiratory Medicine, Department of Internal Medicine, Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ, USA.
Deborah A MeyersDepartment of Medicine, University of Arizona, Tucson, AZ, USA.
Eugene R BleeckerDepartment of Medicine, University of Arizona, Tucson, AZ, USA.
Stacey B GabrielBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Namrata GuptaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Albert Vernon SmithDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-1942-5845
Jian'an LuanMRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-3137-6337
Jing-Hua ZhaoDepartment of Public and Primary Care, Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.
Ailin F HansenK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU Norwegian University of Science and Technology, Trondheim, Norway.
Arnulf LanghammerHUNT Research Centre, Department of Public Health and Nursing, NTNU Norwegian University of Science and Technology, Levanger, Norway.ORCID http://orcid.org/0000-0001-5296-6673
Cristen WillerDivision of Cardiology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-5645-4966
Laxmi BhattaK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU Norwegian University of Science and Technology, Trondheim, Norway.
David PorteousCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-1249-6106
Blair H SmithDivision of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.ORCID http://orcid.org/0000-0002-5362-9430
Archie CampbellCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-0198-5078
Tamar SoferDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8520-8860
Jiwon LeeDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4079-7494
Martha L DaviglusInstitute for Minority Health Research, University of Illinois at Chicago, Chicago, IL, USA.
Bing YuHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Elise LimDepartment of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8967-8464
Hanfei XuDepartment of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
George T O'ConnorPulmonary Center, School of Medicine, Boston University, Boston, MA, USA.
Gaurav TharejaBioinformatics Core, Weill Cornell Medicine-Qatar, Education City, Doha, Qatar.ORCID http://orcid.org/0000-0003-2277-6400
Omar M E AlbaghaCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.ORCID http://orcid.org/0000-0001-5916-5983
Qatar Genome Program Research (QGPR) Consortium
Karsten SuhreBioinformatics Core, Weill Cornell Medicine-Qatar, Education City, Doha, Qatar.ORCID http://orcid.org/0000-0001-9638-3912
Raquel GranellMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-4890-4012
Tariq O FaquihDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0001-8026-2251
Pieter S HiemstraDepartment of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0002-0238-5982
Annelies M SlatsDepartment of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Benjamin H MullinDepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
Jennie HuiBusselton Population Medical Research Institute, QEII Medical Centre, Nedlands, Western Australia, Australia.
Alan JamesBusselton Population Medical Research Institute, QEII Medical Centre, Nedlands, Western Australia, Australia.
John BeilbySchool of Biomedical Sciences, University of Western Australia, Crawley, Western Australia, Australia.
Karina PatasovaDepartment of Twin Research and Genetic Epidemiology, King's College London School of Medicine, London, UK.
Pirro HysiDepartment of Twin Research and Genetic Epidemiology, King's College London School of Medicine, London, UK.ORCID http://orcid.org/0000-0001-5752-2510
Jukka T KoskelaInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-0154-7222
Annah B WyssEpidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA.
Jianping JinWestat, Durham, NC, USA.ORCID http://orcid.org/0000-0002-3774-1609
Sinjini SikdarEpidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA.ORCID http://orcid.org/0000-0003-1230-5162
Mikyeong LeeEpidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA.ORCID http://orcid.org/0000-0002-3036-3684
Sebastian May-WilsonCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-2668-5717
Nicola PirastuCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Katherine A KentistouCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Peter K JoshiCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-6361-5059
Paul R H J TimmersCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-5197-1267
Alexander T WilliamsDepartment of Population Health Sciences, University of Leicester, Leicester, UK.
Robert C FreeLeicester National Institute for Health and Care Research, Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Xueyang WangLeicester National Institute for Health and Care Research, Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
John L MorrisonDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Frank D GillilandDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-9033-7269
Zhanghua ChenDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Carol A WangSchool of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, New South Wales, Australia.ORCID http://orcid.org/0000-0002-4301-3974
Rachel E FoongWal-yan Respiratory Research Centre, Telethon Kids Institute, Perth, Western Australia, Australia.
Sarah E HarrisLothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-4941-5106
Adele TaylorLothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Paul RedmondLothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK.
James P CookDepartment of Health Data Science, University of Liverpool, Liverpool, UK.
Anubha MahajanWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-5585-3420
Lars LindDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Teemu PalviainenInstitute for Molecular Medicine Finland-FIMM, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-7847-8384
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Olli T RaitakariDepartment of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
Jaakko KaprioInstitute for Molecular Medicine Finland-FIMM, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-3716-2455
Taina RantanenFaculty of Sport and Health Sciences, University of Jyvaskyla, Jyvaskyla, Finland.
Kirsi H PietiläinenObesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-8522-1288
Simon R CoxLothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-4036-3642
Craig E PennellSchool of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, New South Wales, Australia.ORCID http://orcid.org/0000-0002-0937-6165
Graham L HallWal-yan Respiratory Research Centre, Telethon Kids Institute, Perth, Western Australia, Australia.
W James GaudermanDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Chris BrightlingLeicester National Institute for Health and Care Research, Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
James F WilsonCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0001-5751-9178
Tuula VasankariFILHA-Finnish Lung Health Association, Helsinki, Finland.ORCID http://orcid.org/0000-0002-1413-8970
Tarja LaitinenAdministration Center, Tampere University Hospital and University of Tampere, Tampere, Finland.
Veikko SalomaaDepartment of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.ORCID http://orcid.org/0000-0001-7563-5324
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Nicholas J TimpsonMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-7141-9189
Eleftheria ZegginiWellcome Sanger Institute, Cambridge, UK.
Josée DupuisDepartment of Epidemiology, Biostatistics, and Occupational Health, School of Population and Global Health, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0003-2871-3603
Caroline HaywardMedical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Ben BrumptonHUNT Research Centre, Department of Public Health and Nursing, NTNU Norwegian University of Science and Technology, Levanger, Norway.ORCID http://orcid.org/0000-0002-3058-1059
Claudia LangenbergMRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-5017-7344
Stefan WeissInterfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-3553-4315
Georg HomuthInterfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0001-6839-0605
Carsten Oliver SchmidtInstitute for Community Medicine, SHIP-Clinical Epidemiological Research, University Medicine Greifswald, Greifswald, Germany.
Nicole Probst-HenschDepartment of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
Marjo-Riitta JarvelinMRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-2149-0630
Alanna C MorrisonHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6381-4296
Ozren PolasekSchool of Medicine, University of Split, Split, Croatia.
Igor RudanCentre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0001-6993-6884
Joo-Hyeon LeeJeffrey Cheah Biomedical Centre, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-7364-6422
Ian SayersDivision of Respiratory Medicine and NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK.ORCID http://orcid.org/0000-0001-5601-5410
Emma L RawlinsWellcome Trust-CRUK Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-7426-3792
Frank DudbridgeDepartment of Population Health Sciences, University of Leicester, Leicester, UK.ORCID http://orcid.org/0000-0002-8817-8908
Edwin K SilvermanChanning Division of Network Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
David P StrachanPopulation Health Research Institute, St George's University of London, London, UK.ORCID http://orcid.org/0000-0001-7854-1366
Robin G WaltersNuffield Department of Population Health, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-9179-0321
Andrew P MorrisCentre for Genetics and Genomics Versus Arthritis, Division of Musculoskeletal and Dermatological Sciences, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-6805-6014
Stephanie J LondonEpidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA.ORCID http://orcid.org/0000-0003-4911-5290
Michael H ChoChanning Division of Network Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4907-1657
Louise V WainDepartment of Population Health Sciences, University of Leicester, Leicester, UK.ORCID http://orcid.org/0000-0003-4951-1867
Ian P Hall *Division of Respiratory Medicine and NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK.ORCID http://orcid.org/0000-0001-9933-3216
Martin D Tobin *Department of Population Health Sciences, University of Leicester, Leicester, UK. martin.tobin@leicester.ac.uk.ORCID http://orcid.org/0000-0002-3596-7874
Qatar Airways (Qatar) · QAUniversity of Leicester · GBQatar Foundation · QABrigham and Women's Hospital · USUniversity of Southern California · USUniversitätsmedizin Greifswald · DENational Institutes of Health · USUniversity of Nottingham · GBNorwegian University of Science and Technology · NOSwiss Tropical and Public Health Institute · CHBoston University · USColumbia University Irving Medical Center · USGhent University Hospital · BELeiden University Medical Center · NLNHS Lothian · GBThe University of Western Australia · AUUniversity of Helsinki · FIBroad Institute · USHelmholtz Zentrum München · DEUniversity of Cambridge · GB

Funding

Statistical Methods for Integrative Genomics in CancerP01CA196569 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Paul Marjoram · 2016 to 2026
$25.5M
Genetic Epidemiology of COPDU01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2007 to 2021
$20.7M
Pulmonary microvascular perfusion in the Multi-Ethnic Study of AtherosclerosisR01HL077612 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI R Graham BARR · 2004 to 2026
$18.8M
Pulmonary Vascular Changes in Early Chronic Obstructive Pulmonary Disease (COPD)R01HL093081 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI R Graham BARR · 2008 to 2026
$17.2M
Pilot Program CoreP30ES027792 · NIEHS · UNIVERSITY OF CHICAGO · PI Gokhan M. Mutlu, Gail S Prins · 2017 to 2026
$13.6M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Genetics and Environment in Adult Respiratory, Allergic and Cardiac diseaseZIAES043012 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI LONDON, STEPHANIE · 2009 to 2025
$6.4M
Leveraging Variant-perturbed Gene Regulation to Support Precision Medicine in COPDR01HL155749 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Kimberly Renee Glass · 2022 to 2026
$4.2M
Integrative genomic, transcriptomic and proteomic studies of pulmonary function and COPDR01HL153248 · NHLBI · UNIVERSITY OF VIRGINIA · PI CHO, MICHAEL H., MANICHAIKUL, ANI WANG · 2021 to 2024
$2.8M
Genomic and Transcriptomic Analysis of Emphysema and Subclinical ILDR01HL131565 · NHLBI · UNIVERSITY OF VIRGINIA · PI MANICHAIKUL, ANI WANG · 2016 to 2020
$2.0M
Multi-omic Subtyping of Chronic Obstructive Pulmonary DiseaseK08HL136928 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI HOBBS, BRIAN DANIEL · 2017 to 2021
$864k
Hypercoagulability and Chronic Lung Disease in Older AdultsK23HL130627 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI OELSNER, ELIZABETH · 2016 to 2019
$686k
Medical Research Council G0600705Medical Research Council G0902313Medical Research Council G1000861Medical Research Council G1002319Medical Research Council MC_PC_14135Medical Research Council MC_PC_17230Medical Research Council MC_PC_19004Medical Research Council MC_U137686851Medical Research Council MC_UU_00006/1Medical Research Council MC_UU_00007/10Medical Research Council MC_UU_00017/1Medical Research Council MR/N003284/1Medical Research Council MR/N011317/1Medical Research Council MR/P00167X/1Medical Research Council MR/P009581/1Medical Research Council MR/S003762/1Medical Research Council MR/S019669/1Medical Research Council MR/S025340/1NCI NIH HHS P01 CA196569NHLBI NIH HHS K08 HL136928NHLBI NIH HHS K23 HL130627NHLBI NIH HHS R01 HL077612NHLBI NIH HHS R01 HL093081NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL131565NHLBI NIH HHS R01 HL153248NHLBI NIH HHS R01 HL155749NHLBI NIH HHS R21 HL129924NHLBI NIH HHS R21 HL153700NHLBI NIH HHS U01 HL089856NIEHS NIH HHS P30 ES027792Wellcome Trust 212946/Z/18/Z
6 · The paper itself

Abstract

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.

Indexed as

LungPulmonary Disease, Chronic ObstructiveGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideSmoking

Identifiers

PMID36914875
PMCPMC10011137
OpenAlexW4324045235

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LicenceCC BY
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identifiers read1
Read underepoch 390

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.