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Resequencing Study Confirms That Host Defense and Cell Senescence Gene Variants Contribute to the Risk of Idiopathic Pulmonary Fibrosis
C. Moore, RZ. Blumhagen, IV. Yang, A. Walts, J. Powers, T. Walker, M. Bishop, P. Russell, B. Vestal, J. Cardwell, CR. Markin, SK. Mathai, MI. Schwarz, MP. Steele, J. Lee, KK. Brown, JE. Loyd, JD. Crapo, EK. Silverman, MH. Cho, JA. James, JM....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
P01 HL092870
NHLBI NIH HHS - United States
U54 GM104938
NIGMS NIH HHS - United States
P30 AR053483
NIAMS NIH HHS - United States
MR/N005953/1
Medical Research Council - United Kingdom
P30 AR073750
NIAMS NIH HHS - United States
R01 HL097163
NHLBI NIH HHS - United States
UL1 RR024975
NCRR NIH HHS - United States
R33 HL120770
NHLBI NIH HHS - United States
U19 AI082714
NIAID NIH HHS - United States
K08 HL130595
NHLBI NIH HHS - United States
NLK
Free Medical Journals
od 1997-07-01 do Před 1 rokem
Freely Accessible Science Journals
od 1997 do Před 1 rokem
ProQuest Central
od 2003-02-01 do 2019-09-15
Open Access Digital Library
od 1998-01-01
Nursing & Allied Health Database (ProQuest)
od 2003-02-01 do 2019-09-15
Health & Medicine (ProQuest)
od 2003-02-01 do 2019-09-15
Public Health Database (ProQuest)
od 2003-02-01 do 2019-09-15
- MeSH
- ABC transportéry genetika MeSH
- celogenomová asociační studie MeSH
- DNA-helikasy genetika MeSH
- exoribonukleasy genetika MeSH
- genetická predispozice k nemoci MeSH
- genetická variace MeSH
- idiopatická plicní fibróza genetika MeSH
- interakce hostitele a patogenu genetika MeSH
- lidé MeSH
- logistické modely MeSH
- mucin 5B genetika MeSH
- promotorové oblasti (genetika) genetika MeSH
- protein A asociovaný s plicním surfaktantem genetika MeSH
- protein C asociovaný s plicním surfaktantem genetika MeSH
- proteiny aktivující GTPasu genetika MeSH
- proteiny vázající telomery genetika MeSH
- RNA genetika MeSH
- sekvenční analýza DNA MeSH
- stárnutí buněk genetika MeSH
- studie případů a kontrol MeSH
- telomerasa genetika MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Rationale: Several common and rare genetic variants have been associated with idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung. Objectives: To develop an integrated understanding of the rare and common variants located in multiple loci that have been reported to contribute to the risk of disease. Methods: We performed deep targeted resequencing (3.69 Mb of DNA) in cases (n = 3,624) and control subjects (n = 4,442) across genes and regions previously associated with disease. We tested for associations between disease and 1) individual common variants via logistic regression and 2) groups of rare variants via sequence kernel association tests. Measurements and Main Results: Statistically significant common variant association signals occurred in all 10 of the regions chosen based on genome-wide association studies. The strongest risk variant is the MUC5B promoter variant rs35705950, with an odds ratio of 5.45 (95% confidence interval, 4.91-6.06) for one copy of the risk allele and 18.68 (95% confidence interval, 13.34-26.17) for two copies of the risk allele (P = 9.60 × 10-295). In addition to identifying for the first time that rare variation in FAM13A is associated with disease, we confirmed the role of rare variation in the TERT and RTEL1 gene regions in the risk of IPF, and found that the FAM13A and TERT regions have independent common and rare variant signals. Conclusions: A limited number of common and rare variants contribute to the risk of idiopathic pulmonary fibrosis in each of the resequencing regions, and these genetic variants focus on biological mechanisms of host defense and cell senescence.
Advanced Lung Disease and Transplant Program Inova Fairfax Hospital Falls Church Virginia
Alfred Hospital and Monash University Melbourne Australia
Asan Medical Center University of Ulsan College of Medicine Seoul Korea
Biomedical Genomics Center University of Minnesota
Biomedical Research Centre University of Nottingham Nottingham United Kingdom
Brigham and Women's Hospital Harvard School of Medicine Boston Massachusetts
CardioPulmonary Reserach Center Alliance Pulmonary Group Guaynabo Puerto Rico
Cork University Hospital and University College Cork Cork Ireland
Department of Diseases of the Thorax Ospedale GB Morgagni Forlì Italy
Department of Internal Medicine University of Genoa Genoa Italy
Department of Medicine and 20 Helmholtz Zentrum München Neuherberg Germany
Department of Medicine and 41 Tokyo Medical and Dental University Tokyo Japan
Department of Medicine Columbia University Irving Medical Center New York New York
Department of Medicine Tallaght University Hospital Trinity College Dublin Dublin Ireland
Department of Medicine University of Alabama at Birmingham Birmingham Alabama
Department of Medicine University of California San Francisco San Francisco California
Department of Medicine University of Chicago Chicago Illinois
Department of Medicine University of Virginia Charlottesville Virginia
Department of Medicine Vanderbilt University School of Medicine Nashville Tennessee
Department of Medicine Warren Alpert Medical School of Brown University Providence Rhode Island
Department of Pulmonary Medicine Gazi University School of Medicine Ankara Turkey
Department of Pulmonology Ege University Hospital Bornova Izmir Turkey
Department of Respiratory Diseases and Allergy Aarhus University Hospital Aarhus Denmark
Division of Pulmonary and Critical Care Medicine Massachusetts General Hospital Boston Massachusetts
Gilead Sciences Foster City California
Helmholtz Zentrum München Neuherberg Germany
Institute for Respiratory Health and
Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas México City México
MRC Centre for Inflammation Research University of Edinburgh Edinburgh United Kingdom
National Hospital Organization Kinki Chuo Chest Medical Center Osaka Japan
National Hospital Organization Tokyo National Hospital Tokyo Japan
National Jewish Health Denver Colorado
National Jewish Health Denver Colorado 2 School of Public Health
National Jewish Health Denver Colorado 2 School of Public Health 3 Department of Medicine and
National Jewish Health Denver Colorado 3 Department of Medicine and
National University Hospital of Iceland University of Iceland Reykjavik Iceland
Northwest Genomics Center University of Washington Seattle Washington
Oklahoma Medical Research Foundation Oklahoma City Oklahoma
Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania
Pulmonary Medicine GB Morgagni Hospital Forlì Italy
Respiratory Department University Hospital of Bellvitge University of Barcelona Barcelona Spain
Respiratory Medicine Unit Royal Infirmary of Edinburgh Edinburgh United Kingdom
Royal Brompton Hospital and Imperial College London United Kingdom
Royal Prince Alfred Hospital and University of Sydney Sydney Australia
Ruhrlandklinik University Hospital University of Duisburg Essen Essen Germany
Simmons Center for Interstitial Lung Disease University of Pittsburgh Pittsburgh Pennsylvania
Tokyo Medical and Dental University Tokyo Japan
Universidad Nacional Autónoma de México México City México
Université Paris Diderot and Hôpital Bichat Paris France
Citace poskytuje Crossref.org
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- $a Resequencing Study Confirms That Host Defense and Cell Senescence Gene Variants Contribute to the Risk of Idiopathic Pulmonary Fibrosis / $c C. Moore, RZ. Blumhagen, IV. Yang, A. Walts, J. Powers, T. Walker, M. Bishop, P. Russell, B. Vestal, J. Cardwell, CR. Markin, SK. Mathai, MI. Schwarz, MP. Steele, J. Lee, KK. Brown, JE. Loyd, JD. Crapo, EK. Silverman, MH. Cho, JA. James, JM. Guthridge, JD. Cogan, JA. Kropski, JJ. Swigris, C. Bair, DS. Kim, W. Ji, H. Kim, JW. Song, LA. Maier, KA. Pacheco, N. Hirani, AS. Poon, F. Li, RG. Jenkins, R. Braybrooke, G. Saini, TM. Maher, PL. Molyneaux, P. Saunders, Y. Zhang, KF. Gibson, DJ. Kass, M. Rojas, J. Sembrat, PJ. Wolters, HR. Collard, JS. Sundy, T. O'Riordan, ME. Strek, I. Noth, SF. Ma, MK. Porteous, ME. Kreider, NB. Patel, Y. Inoue, M. Hirose, T. Arai, S. Akagawa, O. Eickelberg, IE. Fernandez, J. Behr, N. Mogulkoc, TJ. Corte, I. Glaspole, S. Tomassetti, C. Ravaglia, V. Poletti, B. Crestani, R. Borie, C. Kannengiesser, H. Parfrey, C. Fiddler, D. Rassl, M. Molina-Molina, C. Machahua, AM. Worboys, G. Gudmundsson, HJ. Isaksson, DJ. Lederer, AJ. Podolanczuk, SB. Montesi, E. Bendstrup, V. Danchel, M. Selman, A. Pardo, MT. Henry, MP. Keane, P. Doran, M. Vašáková, M. Sterclova, CJ. Ryerson, PG. Wilcox, T. Okamoto, H. Furusawa, Y. Miyazaki, G. Laurent, S. Baltic, C. Prele, Y. Moodley, BS. Shea, K. Ohta, M. Suzukawa, O. Narumoto, SD. Nathan, DC. Venuto, ML. Woldehanna, N. Kokturk, JA. de Andrade, T. Luckhardt, T. Kulkarni, F. Bonella, SC. Donnelly, A. McElroy, ME. Armstong, A. Aranda, RG. Carbone, F. Puppo, KB. Beckman, DA. Nickerson, TE. Fingerlin, DA. Schwartz,
- 520 9_
- $a Rationale: Several common and rare genetic variants have been associated with idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung. Objectives: To develop an integrated understanding of the rare and common variants located in multiple loci that have been reported to contribute to the risk of disease. Methods: We performed deep targeted resequencing (3.69 Mb of DNA) in cases (n = 3,624) and control subjects (n = 4,442) across genes and regions previously associated with disease. We tested for associations between disease and 1) individual common variants via logistic regression and 2) groups of rare variants via sequence kernel association tests. Measurements and Main Results: Statistically significant common variant association signals occurred in all 10 of the regions chosen based on genome-wide association studies. The strongest risk variant is the MUC5B promoter variant rs35705950, with an odds ratio of 5.45 (95% confidence interval, 4.91-6.06) for one copy of the risk allele and 18.68 (95% confidence interval, 13.34-26.17) for two copies of the risk allele (P = 9.60 × 10-295). In addition to identifying for the first time that rare variation in FAM13A is associated with disease, we confirmed the role of rare variation in the TERT and RTEL1 gene regions in the risk of IPF, and found that the FAM13A and TERT regions have independent common and rare variant signals. Conclusions: A limited number of common and rare variants contribute to the risk of idiopathic pulmonary fibrosis in each of the resequencing regions, and these genetic variants focus on biological mechanisms of host defense and cell senescence.
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