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Title: Overlap of genetic risk between interstitial lung abnormalities and idiopathic pulmonary fibrosis
Authors: Hobbs, Brian D.
Putman, Rachel K.
Araki, Tetsuro
Nishino, Mizuki
Gudmundsson, Gunnar
Gudnason, Vilmundur
Eiriksdottir, Gudny
Nogueira, Nuno Rodrigues Zilhao
Dupuis, Josée
Xu, Hanfei
O’Connor, George T.
Manichaikul, Ani
Nguyen, Jennifer
Podolanczuk, Anna J.
Madahar, Purnema
Rotter, Jerome I.
Lederer, David J.
Barr, R. Graham
Rich, Stephen S.
Ampleford, Elizabeth J.
Ortega, Victor E.
Peters, Stephen P.
O’Neal, Wanda K.
Newell Jr., John D.
Bleecker, Eugene R.
Meyers, Deborah A.
Allen, Richard J.
Oldham, Justin M.
Ma, Shwu-Fan
Noth, Imre
Jenkins, R. Gisli
Maher, Toby M.
Hubbard, Richard B.
Wain, Louise V.
Fingerln, Tasha E.
Schwartz, David A.
Washko, George R.
Rosas, Ivan O.
Silverman, Edwin K.
Hatabu, Hiroto
Cho, Michael H.
Hunninghake, Gary M.
COPDGene Investigators
ECLIPSE Investigators
SPIROMICS Research Group
UK ILD Consortium
First Published: 2019
Publisher: American Thoracic Society
Citation: American Journal of Respiratory and Critical Care Medicine, 2019, In Press
Abstract: Rationale Interstitial lung abnormalities (ILA) are associated with the highest genetic risk locus for IPF; however, the extent to which there is additional overlap with IPF, or unique associations among those with ILA is not known. Objectives To perform a genome-wide association study (GWAS) of ILA. Methods: ILA and the subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES, COPDGene, Framingham Heart, ECLIPSE, MESA, and SPIROMICS studies. We performed a GWAS of ILA 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 in 1,699 ILA cases and 10,274 controls. The MUC5B promoter variant rs35705950 was significantly associated with both ILA (p=2.6x10-27) and subpleural ILA (p=1.6x10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, p=3.8x10-8 ) and FCF1P3 (rs73199442, p=4.8x10-8 ) with ILA, and HTRE1 (rs7744971, p=4.2x10-8 ) with subpleural-predominant ILA. These novel associations were not associated with IPF. Of 12 previously reported IPF GWAS loci, 5 (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (p<0.05/12) with ILA. Conclusions In a GWAS of ILA in six studies, we confirmed the association with a MUC5B 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 and suggest distinct genetically-driven biologic pathways between ILA and IPF.
ISSN: 1073-449X
Links: TBA
Embargo on file until: 1-Jan-10000
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2019, American Thoracic Society. Deposited with reference to the publisher’s open access archiving policy. (
Description: This article has an online data supplement, which is accessible from this issue’s table of content online at
The file associated with this record is under embargo until publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Health Sciences

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