Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis
| Autor: | Mizuki Nishino, Shwu Fan Ma, John D. Newell, Brian D. Hobbs, Purnema Madahar, Ani Manichaikul, Deborah A. Meyers, Vilmundur Gudnason, Tetsuro Araki, Gunnar Gudmundsson, Anna J. Podolanczuk, R. Graham Barr, David J. Lederer, George R. Washko, Victor E. Ortega, Justin M. Oldham, R. Gisli Jenkins, David A. Schwartz, Jerome I. Rotter, Gudny Eiriksdottir, Hanfei Xu, Stephen S. Rich, Louise V. Wain, Toby M. Maher, Imre Noth, Stephen P. Peters, Michael H. Cho, Tasha E. Fingerlin, Rachel K. Putman, Richard J. Allen, Hiroto Hatabu, Elizabeth J. Ampleford, George T. O'Connor, Wanda K. O'Neal, Josée Dupuis, Ivan O. Rosas, Gary M. Hunninghake, Nuno Rodrigues Zilhao Nogueira, Eugene R. Bleecker, Jennifer N. Nguyen, Richard Hubbard, Edwin K. Silverman |
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| Přispěvatelé: | National Institute for Health Research, British Lung Foundation |
| Rok vydání: | 2019 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Pathology Respiratory System SNP Genome-wide association study Single-nucleotide polymorphism Critical Care and Intensive Care Medicine 03 medical and health sciences Idiopathic pulmonary fibrosis 0302 clinical medicine interstitial lung abnormalities Risk Factors Fibrosis Epidemiology medicine Humans genetics 030212 general & internal medicine Respiratory system 11 Medical and Health Sciences genome-wide association study Lung business.industry Original Articles single-nucleotide polymorphism respiratory system medicine.disease Idiopathic Pulmonary Fibrosis respiratory tract diseases medicine.anatomical_structure 030228 respiratory system Lung Diseases Interstitial business |
| Zdroj: | Am J Respir Crit Care Med |
| ISSN: | 1535-4970 1073-449X |
| Popis: | Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known. Objectives: To perform a genome-wide association study (GWAS) of ILAs. Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF. Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 × 10(−27)) and subpleural ILAs (P = 1.6 × 10(−29)). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 × 10(−8)) and FCF1P3 (rs73199442, P = 4.8 × 10(−8)) with ILAs, and near HTRE1 (rs7744971, P = 4.2 × 10(−8)) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P |
| Databáze: | OpenAIRE |
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