Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis
| Autor: | Simon P. Hart, Vilmundur Gudnason, Yingze Zhang, Hiroto Hatabu, Rebecca Braybrooke, R. Gisli Jenkins, Shwu-Fan Ma, Michael Ng, Carlos Flores, George T. O'Connor, Ma'en Obeidat, Nik Hirani, Brian D. Hobbs, Megan L. Paynton, Amy Dressen, Ayodeji Adegunsoye, Helen Booth, Dominic Furniss, Philippe Joubert, Eunice Oballa, Ian Sayers, Martin D. Tobin, Krina T. Zondervan, Richard Hubbard, Xuan Li, Yohan Bossé, John D. Newell, Beatriz Guillen-Guio, Ann B. Millar, Wim Timens, Mary E. Strek, Gunnar Gudmundsson, Philip L. Molyneaux, Gary M. Hunninghake, Ani Manichaikul, Tasha E. Fingerlin, Rachel K. Putman, Richard J. Allen, Vidyia Navaratnam, Maria Molina-Molina, Don D. Sin, Helen Parfrey, Luke M. Kraven, Moira K. B. Whyte, Xuting R. Sheng, Phuwanat Sakornsakolpat, David J. Lederer, David C. Nickle, Ian P. Hall, Brian L. Yaspan, Louise V. Wain, Toby M. Maher, Gauri Saini, Ke Hao, Michael Hill, Naftali Kaminski, Andrew P. Morris, Hanfei Xu, Justin M. Oldham, David A. Schwartz, Robin J. McAnulty, Michael H. Cho, Victor E. Ortega, Margaret Neighbors, Imre Noth, William A. Fahy |
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| Přispěvatelé: | Action for Pulmonary Fibrosis, National Institute for Health Research, British Lung Foundation, Groningen Research Institute for Asthma and COPD (GRIAC), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Pathology Epidemiology Respiratory System Kinesins Gene Expression Genome-wide association study Cell Cycle Proteins TOR Serine-Threonine Kinases/metabolism VARIANTS Critical Care and Intensive Care Medicine Idiopathic pulmonary fibrosis 0302 clinical medicine KIF15 TELOMERES genetics 030212 general & internal medicine Respiratory system 11 Medical and Health Sciences RISK TOR Serine-Threonine Kinases Intracellular Signaling Peptides and Proteins respiratory system Middle Aged MAD1L1 3. Good health medicine.anatomical_structure SURVIVAL epidemiology Female Life Sciences & Biomedicine Kinesin/genetics Signal Transduction Pulmonary and Respiratory Medicine medicine.medical_specialty Spindle Apparatus DIAGNOSIS Risk Assessment REGION 03 medical and health sciences Critical Care Medicine General & Internal Medicine medicine Genetics Erfðafræði Humans Genetic Predisposition to Disease Aged Cell Cycle Proteins/genetics Lungnasjúkdómar Lung Science & Technology DEPTOR business.industry MUTATIONS Case-control study Editorials RTEL1 medicine.disease Epithelium Idiopathic Pulmonary Fibrosis respiratory tract diseases Genarannsóknir 030228 respiratory system EVENT Case-Control Studies GAIN business Intracellular Signaling Peptides and Proteins/genetics Idiopathic Pulmonary Fibrosis/genetics Genome-Wide Association Study |
| Zdroj: | Allen, R J, Guillen-guio, B, Oldham, J M, Ma, S, Dressen, A, Paynton, M L, Kraven, L M, Obeidat, M, Li, X, Ng, M, Braybrooke, R, Molina-molina, M, Hobbs, B D, Putman, R K, Sakornsakolpat, P, Booth, H L, Fahy, W A, Hart, S P, Hill, M R, Hirani, N, Hubbard, R B, Mcanulty, R J, Millar, A B, Navaratnam, V, Oballa, E, Parfrey, H, Saini, G, Whyte, M K B, Zhang, Y, Kaminski, N, Adegunsoye, A, Strek, M E, Neighbors, M, Sheng, X R, Gudmundsson, G, Gudnason, V, Hatabu, H, Lederer, D J, Manichaikul, A, Newell Jr., J D, O'connor, G T, Ortega, V E, Xu, H, Fingerlin, T E, Bossé, Y, Hao, K, Joubert, P, Nickle, D C, Sin, D D, Timens, W, Furniss, D, Morris, A P, Zondervan, K, Hall, I P, Sayers, I, Tobin, M D, Maher, T M, Cho, M H, Hunninghake, G M, Schwartz, D A, Yaspan, B L, Molyneaux, P L, Flores, C, Noth, I, Jenkins, R G & Wain, L V 2020, ' Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis ', American Journal of Respiratory and Critical Care Medicine, vol. 201, no. 5, pp. 564-574 . https://doi.org/10.1164/rccm.201905-1017OC AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE American Journal of Respiratory and Critical Care Medicine, 201(5), 564-574. AMER THORACIC SOC Allen, R J, Guillen-Guio, B, Oldham, J M, Ma, S-F, Dressen, A, Paynton, M L, Kraven, L M, Obeidat, M, Li, X, Ng, M, Braybrooke, R, Molina-Molina, M, Hobbs, B D, Putman, R K, Sakornsakolpat, P, Booth, H L, Fahy, W A, Hart, S P, Hill, M R, Hirani, N, Hubbard, R B, McAnulty, R J, Millar, A B, Navaratnam, V, Oballa, E, Parfrey, H, Saini, G, Whyte, M K B, Zhang, Y, Kaminski, N, Adegunsoye, A, Strek, M E, Neighbors, M, Sheng, X R, Gudmundsson, G, Gudnason, V, Hatabu, H, Lederer, D J, Manichaikul, A, Newell, J D, O'Connor, G T, Ortega, V E, Xu, H, Fingerlin, T E, Bossé, Y, Hao, K, Joubert, P, Nickle, D C, Sin, D D, Timens, W, Furniss, D, Morris, A P, Zondervan, K, Hall, I P, Sayers, I, Tobin, M D, Maher, T M, Cho, M H, Hunninghake, G M, Schwartz, D A, Yaspan, B L, Molyneaux, P L, Flores, C, Noth, I, Jenkins, R G & Wain, L V 2019, ' Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis ', American Journal of Respiratory and Critical Care Medicine . https://doi.org/10.1164/rccm.201905-1017OC American Journal of Respiratory and Critical Care Medicine |
| ISSN: | 1073-449X |
| Popis: | Publisher's version (útgefin grein) Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterized by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. Genome-wide association studies have reported signals of association implicating multiple pathways including host defense, telomere maintenance, signaling, and cell-cell adhesion. Objectives: To improve our understanding of factors that increase IPF susceptibility by identifying previously unreported genetic associations. Methods: We conducted genome-wide analyses across three independent studies and meta-analyzed these results to generate the largest genome-wide association study of IPF to date (2,668 IPF cases and 8,591 controls). We performed replication in two independent studies (1,456 IPF cases and 11,874 controls) and functional analyses (including statistical fine-mapping, investigations into gene expression, and testing for enrichment of IPF susceptibility signals in regulatory regions) to determine putatively causal genes. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF. Measurements and Main Results: We identified and replicated threenewgenome-wide significant (P R.J.A. is an Action for Pulmonary Fibrosis Research Fellow. L.V.W. holds a GSK/British Lung Foundation Chair in Respiratory Research. R.G.J. is supported by a National Institute for Health Research (NIHR) Research Professorship (NIHR reference RP-2017-08-ST2-014). I.N. is supported by the NHLBI (R01HL130796). B.G.-G. is funded by Agencia Canaria de Investigación, Innovación y Sociedad de la Información (TESIS2015010057) cofunded by European Social Fund. J.M.O. is supported by the NHLBI (K23HL138190). C.F. is supported by the Spanish Ministry of Science, Innovation and Universities (grant RTC-2017-6471-1; Ministerio de Ciencia e Innovacion/Agencia Estatal de Investigación/Fondo Europeo de Desarrollo Regional, Unión Europea) cofinanced by the European Regional Development Funds “A way of making Europe” from the European Union and by agreement OA17/008 with Instituto Tecnológico y de Energías Renovables to strengthen scientific and technological education, training, research, development and innovation in Genomics, Personalized Medicine and Biotechnology. The Spain Biobank array genotyping service was performed at CEGEN-PRB3-ISCIII, which is supported by PT17/0019, of the PE I+D+i 2013–2016, funded by Instituto de Salud Carlos III, and cofinanced by the European Regional Development Funds. P.L.M. is an Action for Pulmonary Fibrosis Research Fellow. M.O. is a fellow of the Parker B. Francis Foundation and a Scholar of the Michael Smith Foundation for Health Research. B.D.H. is supported by NIH K08 HL136928, Parker B. Francis Research Opportunity Award. M.H.C. and G.M.H. are supported by NHLBI grants R01HL113264 (M.H.C.), R01HL137927 (M.H.C.), R01HL135142 (M.H.C. and G.M.H.), R01111024 (G.M.H.), and R01130974 (G.M.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funding body has no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. T.M.M. is supported by an NIHR Clinician Scientist Fellowship (NIHR Ref: CS-2013-13-017) and a British Lung Foundation Chair in Respiratory Research (C17-3). M.D.T. is supported by a Wellcome Trust Investigator Award (WT202849/Z/16/Z). The research was partially supported by the NIHR Leicester Biomedical Research Centre; the views expressed are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR, or the Department of Health. I.P.H. was partially supported by the NIHR Nottingham Biomedical Research Centre; the views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. I.S. is supported by Medical Research Council (G1000861) and Asthma UK (AUK-PG-2013-188). D.F. was supported by an Intermediate Fellowship from the Wellcome Trust (097152/Z/11/Z). This work was partially supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. V.N. is funded by an NIHR Clinical Lectureship. G.G. is supported by project grant 141513-051 from the Icelandic Research Fund and Landspitali Scientific Fund A-2016-023, A-2017-029, and A-2018-025. D.J.L. and A.M. are supported by Multi-Ethnic Study of Atherosclerosis (MESA) and the MESA SNP Health Association Resource (SHARe) project are conducted and supported by the NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, California) and the Broad Institute of Harvard and Massachusetts Institute of Technology (Boston, Massachusetts) using the Affymetrix Genome-Wide Human SNP Array 6.0. This work was supported by NIH grants R01 HL131565 (A.M.), R01 HL103676 (D.J.L.), and R01 HL137234 (D.J.L.). |
| Databáze: | OpenAIRE |
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