Journal article
Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis
American journal of respiratory and critical care medicine, Vol.200(11), pp.1402-1413
12/01/2019
DOI: 10.1164/rccm.201903-0511oc
PMCID: PMC6884045
PMID: 31339356
Abstract
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.
To perform a genome-wide association study (GWAS) of ILAs.
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.
Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The
(mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (
= 2.6 × 10
) and subpleural ILAs (
= 1.6 × 10
). We discovered novel genome-wide associations near
(rs6886640,
= 3.8 × 10
) and
(rs73199442,
= 4.8 × 10
) with ILAs, and near
(rs7744971,
= 4.2 × 10
) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (
,
,
,
, and
) were significantly associated (
< 0.05/12) with ILAs.
In a GWAS of ILAs in six studies, we confirmed the association with a
promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones.
Details
- Title: Subtitle
- Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis
- Creators
- Brian D Hobbs - Zhejiang MedicineRachel K Putman - Division of Pulmonary and Critical Care Medicine.Tetsuro Araki - Brigham and Women's HospitalMizuki Nishino - Brigham and Women's HospitalGunnar Gudmundsson - Department of Respiratory Medicine, Landspital University Hospital, and.Vilmundur Gudnason - University of IcelandGudny Eiriksdottir - Icelandic Heart AssociationNuno Rodrigues Zilhao Nogueira - Icelandic Heart Association, Kopavogur, IcelandJosée Dupuis - Boston UniversityHanfei Xu - Boston UniversityGeorge T O'Connor - Framingham Heart StudyAni Manichaikul - Center for Public Health Genomics.Jennifer Nguyen - Center for Public Health Genomics.Anna J Podolanczuk - Department of Medicine, College of Physicians and Surgeons, and.Purnema Madahar - Department of Medicine, College of Physicians and Surgeons, and.Jerome I Rotter - Ronald Reagan UCLA Medical CenterDavid J Lederer - Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.R Graham Barr - Columbia UniversityStephen S Rich - Center for Public Health Genomics.Elizabeth J Ampleford - Wake Forest UniversityVictor E Ortega - Wake Forest UniversityStephen P Peters - Wake Forest UniversityWanda K O'Neal - University of North Carolina at Chapel HillJohn D Jr Newell - Department of Radiology, University of Washington, Seattle, WashingtonEugene R Bleecker - University of ArizonaDeborah A Meyers - University of ArizonaRichard J Allen - University of LeicesterJustin M Oldham - University of California, DavisShwu-Fan Ma - University of VirginiaImre Noth - University of VirginiaR Gisli Jenkins - National Institute for Health ResearchToby M Maher - Imperial College LondonRichard B Hubbard - University of NottinghamLouise V Wain - Glenfield HospitalTasha E Fingerlin - National Jewish HealthDavid A Schwartz - University of Colorado DenverGeorge R Washko - Brigham and Women's HospitalIvan O Rosas - Division of Pulmonary and Critical Care Medicine.Edwin K Silverman - Harvard Medical SchoolHiroto Hatabu - Brigham and Women's HospitalMichael H Cho - Zhejiang Medicine (China)Gary M Hunninghake - Brigham and Women's HospitalCOPDGene Investigators
- Contributors
- Eric A Hoffman (Contributor) - University of Iowa, Radiology
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory and critical care medicine, Vol.200(11), pp.1402-1413
- DOI
- 10.1164/rccm.201903-0511oc
- PMID
- 31339356
- PMCID
- PMC6884045
- NLM abbreviation
- Am J Respir Crit Care Med
- ISSN
- 1535-4970
- eISSN
- 1535-4970
- Grant note
- R33 HL120770 / NHLBI NIH HHS R01 CA203636 / NCI NIH HHS U01 HL089897 / NHLBI NIH HHS U01 HL137880 / NHLBI NIH HHS R01 HL131565 / NHLBI NIH HHS P01 HL092870 / NHLBI NIH HHS T32 HL007085 / NHLBI NIH HHS K24 HL137013 / NHLBI NIH HHS MR/N005953/1 / Medical Research Council U01 HL089856 / NHLBI NIH HHS RP-2017-08-ST2-014 / Department of Health R01 HL135142 / NHLBI NIH HHS R01 HL097163 / NHLBI NIH HHS K08 HL140087 / NHLBI NIH HHS R01 HL130974 / NHLBI NIH HHS R01 HL111024 / NHLBI NIH HHS K23 HL140199 / NHLBI NIH HHS K08 HL136928 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/01/2019
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984318714202771
Metrics
24 Record Views