@article {1675356,
	title = {Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis},
	journal = {Am J Respir Crit Care Med},
	volume = {200},
	number = {11},
	year = {2019},
	month = {2019 Dec 01},
	pages = {1402-1413},
	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 {\texttimes} 10-27) and subpleural ILAs (P = 1.6 {\texttimes} 10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 {\texttimes} 10-8) and FCF1P3 (rs73199442, P = 4.8 {\texttimes} 10-8) with ILAs, and near HTRE1 (rs7744971, P = 4.2 {\texttimes} 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 \< 0.05/12) with ILAs.Conclusions: In a GWAS of ILAs 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 genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones.},
	keywords = {Aged, beta Karyopherins, Case-Control Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Idiopathic Pulmonary Fibrosis, Lung Diseases, Interstitial, Male, Middle Aged, Mucin-5B, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, TATA Box Binding Protein-Like Proteins},
	issn = {1535-4970},
	doi = {10.1164/rccm.201903-0511OC},
	author = {Hobbs, Brian D and Putman, Rachel K and Araki, Tetsuro and Nishino, Mizuki and Gudmundsson, Gunnar and Gudnason, Vilmundur and Eiriksdottir, Gudny and Zilhao Nogueira, Nuno Rodrigues and Dupuis, Jos{\'e}e and Xu, Hanfei and O{\textquoteright}Connor, George T and Manichaikul, Ani and Nguyen, Jennifer and Podolanczuk, Anna J and Madahar, Purnema and Rotter, Jerome I and Lederer, David J and Barr, R Graham and Rich, Stephen S and Ampleford, Elizabeth J and Ortega, Victor E and Peters, Stephen P and O{\textquoteright}Neal, Wanda K and Newell, John D and Bleecker, Eugene R and Meyers, Deborah A and Allen, Richard J and Oldham, Justin M and Ma, Shwu-Fan and Noth, Imre and Jenkins, R Gisli and Maher, Toby M and Hubbard, Richard B and Wain, Louise V and Fingerlin, Tasha E and Schwartz, David A and Washko, George R and Rosas, Ivan O and Silverman, Edwin K and Hatabu, Hiroto and Cho, Michael H and Hunninghake, Gary M}
}