دورية أكاديمية
Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.
| العنوان: | Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations. |
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| المؤلفون: | Sakornsakolpat P; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Prokopenko D; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA., Lamontagne M; Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Quebec, Canada., Reeve NF; Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK., Guyatt AL; Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK., Jackson VE; Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK., Shrine N; Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK., Qiao D; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA., Bartz TM; Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.; Department of Medicine, University of Washington, Seattle, WA, USA.; Department of Biostatistics, University of Washington, Seattle, WA, USA., Kim DK; Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, South Korea., Lee MK; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Raleigh, NC, USA., Latourelle JC; Department of Neurology, Boston University School of Medicine, Boston, MA, USA., Li X; Department of Medicine, University of Arizona, Tucson, AZ, USA., Morrow JD; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA., Obeidat M; University of British Columbia Center for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada., Wyss AB; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Raleigh, NC, USA., Bakke P; Department of Clinical Science, University of Bergen, Bergen, Norway., Barr RG; Department of Medicine, College of Physicians and Surgeons and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA., Beaty TH; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA., Belinsky SA; Lovelace Respiratory Research Institute, Albuquerque, NM, USA., Brusselle GG; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.; Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam, the Netherlands., Crapo JD; Division of Pulmonary and Critical Care Medicine, Department of Medicine, National Jewish Health, Denver, CO, USA., de Jong K; University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands., DeMeo DL; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA., Fingerlin TE; Center for Genes, Environment and Health, National Jewish Health, Denver, CO, USA.; Department of Biostatistics and Informatics, University of Colorado Denver, Aurora, CO, USA., Gharib SA; Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Department of Medicine, University of Washington, Seattle, WA, USA., Gulsvik A; Department of Clinical Science, University of Bergen, Bergen, Norway., Hall IP; Division of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.; National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham, UK., Hokanson JE; Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Kim WJ; Department of Internal Medicine and Environmental Health Center, School of Medicine, Kangwon National University, Chuncheon, South Korea., Lomas DA; UCL Respiratory, University College London, London, UK., London SJ; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Raleigh, NC, USA., Meyers DA; Department of Medicine, University of Arizona, Tucson, AZ, USA., O'Connor GT; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA.; Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Rennard SI; Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.; Clinical Discovery Unit, AstraZeneca, Cambridge, UK., Schwartz DA; Department of Medicine, School of Medicine, University of Colorado Denver, Aurora, CO, USA.; Department of Immunology, School of Medicine, University of Colorado Denver, Aurora, CO, USA., Sliwinski P; 2nd Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland., Sparrow D; VA Boston Healthcare System and Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Strachan DP; Population Health Research Institute, St. George's University of London, London, UK., Tal-Singer R; GlaxoSmithKline R&D, Collegeville, PA, USA., Tesfaigzi Y; Lovelace Respiratory Research Institute, Albuquerque, NM, USA., Vestbo J; School of Biological Sciences, University of Manchester, Manchester, UK., Vonk JM; University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands., Yim JJ; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea., Zhou X; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA., Bossé Y; Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Quebec, Canada.; Department of Molecular Medicine, Laval University, Québec, Québec, Canada., Manichaikul A; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.; Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA., Lahousse L; Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.; Department of Bioanalysis, Ghent University, Ghent, Belgium., Silverman EK; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA., Boezen HM; University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands., Wain LV; Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.; National Institute for Health Research Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK., Tobin MD; Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.; National Institute for Health Research Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK., Hobbs BD; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA., Cho MH; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. remhc@channing.harvard.edu.; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA. remhc@channing.harvard.edu. |
| مؤلفون مشاركون: | SpiroMeta Consortium, International COPD Genetics Consortium |
| المصدر: | Nature genetics [Nat Genet] 2019 Mar; Vol. 51 (3), pp. 494-505. Date of Electronic Publication: 2019 Feb 25. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Nature Pub. Co., c1992- |
| مواضيع طبية MeSH: | Genetic Predisposition to Disease/*genetics , Pulmonary Disease, Chronic Obstructive/*genetics, Adult ; Aged ; Asthma/genetics ; Case-Control Studies ; Female ; Gene Expression/genetics ; Genetic Loci/genetics ; Genome-Wide Association Study/methods ; Humans ; Lung/physiopathology ; Male ; Middle Aged ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Pulmonary Fibrosis/genetics ; Smoking/genetics |
| مستخلص: | Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10 -8 ; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD. |
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| معلومات مُعتمدة: | R01 HL113264 United States HL NHLBI NIH HHS; MC_PC_17228 United Kingdom MRC_ Medical Research Council; MR/N024842/1 United Kingdom MRC_ Medical Research Council; G0700704 United Kingdom MRC_ Medical Research Council; R01 HL089856 United States HL NHLBI NIH HHS; P01 HL105339 United States HL NHLBI NIH HHS; G1000861 United Kingdom MRC_ Medical Research Council; R01 HL137927 United States HL NHLBI NIH HHS; United Kingdom WT_ Wellcome Trust; R33 HL120770 United States HL NHLBI NIH HHS; 202849/Z/16/Z United Kingdom WT_ Wellcome Trust; P01 HL132825 United States HL NHLBI NIH HHS; R01 HL111024 United States HL NHLBI NIH HHS; U01 HL089856 United States HL NHLBI NIH HHS; R01 HL135142 United States HL NHLBI NIH HHS; MC_PC_12010 United Kingdom MRC_ Medical Research Council; MC_UU_00007/10 United Kingdom MRC_ Medical Research Council; K08 HL136928 United States HL NHLBI NIH HHS; K01 HL129039 United States HL NHLBI NIH HHS; T32 HL007085 United States HL NHLBI NIH HHS; R01 HL097163 United States HL NHLBI NIH HHS; MR/S003762/1 United Kingdom MRC_ Medical Research Council; MR/N011317/1 United Kingdom MRC_ Medical Research Council; R01 HL084323 United States HL NHLBI NIH HHS; BB/F019394/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; MC_QA137853 United Kingdom MRC_ Medical Research Council; MR/K026992/1 United Kingdom MRC_ Medical Research Council |
| فهرسة مساهمة: | Investigator: N Shrine; AL Guyatt; C Batini; JH Zhao; M Wielscher; S Weiss; KA Kentistou; JP Cook; J Hui; S Karrasch; M Imboden; SE Harris; J Marten; S Enroth; SM Kerr; I Surakka; V Vitart; T Lehtimäki; R Ewert; C Gieger; G Homuth; PK Joshi; C Langenberg; L Lind; J Luan; A Mahajan; A Murray; DJ Porteous; R Rawal; BH Smith; PRHJ Timmers; OT Raitakari; M Kähönen; O Polasek; U Gyllensten; I Rudan; IJ Deary; NM Probst-Hensch; H Schulz; AL James; JF Wilson; B Stubbe; E Zeggini; MR Jarvelin; N Wareham; C Hayward; AP Morris; DP Strachan; IP Hall; MD Tobin; LV Wain; A Agusti; W Anderson; N Bakerly; P Bakke; R Bals; KC Barnes; RG Barr; TH Beaty; ER Bleecker; HM Boezen; Y Bossé; R Bowler; C Brightling; M de Bruijne; PJ Castaldi; B Celli; MH Cho; HO Coxson; JD Crapo; R Crystal; P de Jong; A Dirksen; J Dy; M Foreman; J Garcia-Aymerich; P Gevenois; S Ghosh; H Gietema; A Gulsvik; IP Hall; N Hansel; CP Hersh; BD Hobbs; E Hoffman; N Kalsheker; HU Kauczor; WJ Kim; DK Kim; T Laitinen; D Lambrechts; SD Lee; AA Litonjua; DA Lomas; SJ London; DW Loth; SM Lutz; D Lynch; W MacNee; ML McDonald; DA Meyers; JD Newell; BG Nordestgaard; GT O'Connor; M Obeidat; YM Oh; PD Paré; M Pistolesi; DS Postma; M Puhan; E Regan; SS Rich; JB Seo; A Short; EK Silverman; D Sparrow; B Stoel; DP Strachan; N Sverzellati; R Tal-Singer; G Ter Riet; Y Tesfaigzi; MD Tobin; EJR Van Beek; B van Ginneken; J Vestbo; CF Vogelmeier; LV Wain; A Wanner; G Washko; E Wauters; EFM Wouters; RP Young; L Zeigler-Heitbrock |
| تواريخ الأحداث: | Date Created: 20190227 Date Completed: 20190424 Latest Revision: 20240717 |
| رمز التحديث: | 20240717 |
| مُعرف محوري في PubMed: | PMC6546635 |
| DOI: | 10.1038/s41588-018-0342-2 |
| PMID: | 30804561 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1546-1718 |
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| DOI: | 10.1038/s41588-018-0342-2 |