Back to Search
Start Over
Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis
- Source :
- Am J Respir Crit Care Med
- Publication Year :
- 2019
- Publisher :
- American Thoracic Society, 2019.
-
Abstract
- 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
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15354970 and 1073449X
- Volume :
- 200
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory and Critical Care Medicine
- Accession number :
- edsair.doi.dedup.....cfc7666beb3435bd8826bed3a49004fd