Longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: a genome-wide association study
Richard J. Allen, Justin M. Oldham, David Jenkins, Olivia C. Leavy, Beatriz Guillén‐Guío, Carl Melbourne, Shwu‐Fan Ma, Jonathan Jou, John S. Kim, William A. Fahy, Eunice Oballa, Richard Hubbard, Vidya Navaratnam, Rebecca Braybrooke, Gauri Saini, Katy M. Roach, Martin D. Tobin, Nik Hirani, Moira K. B. Whyte, Naftali Kaminski, Yingze Zhang, Fernando J. Martínez, A. Linderholm, Ayodeji Adegunsoye, Mary E. Strek, Toby M. Maher, Philip L. Molyneaux, Carlos Flores, Imre Noth, Gísli Jenkins, Louise V. Wain
Abstract
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an incurable lung disease characterised by progressive scarring leading to alveolar stiffness, reduced lung capacity, and impeded gas transfer. We aimed to identify genetic variants associated with declining lung capacity or declining gas transfer after diagnosis of IPF. METHODS: when meta-analysing across all discovery and follow-up studies, had consistent direction of effects across all four studies, and were nominally significant (p<0·05) in each study. FINDINGS: ). INTERPRETATION: Our analysis identifies a genetic variant associated with disease progression, which might highlight a new biological mechanism for IPF. We found that PKN2, a Rho and Rac effector protein, is the most likely gene of interest from this analysis. PKN2 inhibitors are currently in development and signify a potential novel therapeutic approach for IPF. FUNDING: Action for Pulmonary Fibrosis, Medical Research Council, Wellcome Trust, and National Institutes of Health National Heart, Lung, and Blood Institute.