Genome-wide association study of idiopathic pulmonary fibrosis susceptibility using clinically curated European ancestry datasets

作者：Daniel Chin, Tamara Hernández-Beeftink, Lauren J. Donoghue, Beatriz Guillén‐Guío, Olivia C. Leavy, Ayodeji Adegunsoye, Helen Booth, CleanUP-IPF Investigators of the Pulmonary Trials Cooperative, William A. Fahy, Tasha E. Fingerlin, Bibek Gooptu, Ian P. Hall, Simon Paul Hart, Mike R. Hill, Nik Hirani, Simon R. Johnson, Naftali Kaminski, Jose Miguel Lorenzo-Salazar, Shwu‐Fan Ma, Robin J. McAnulty, Mark I. McCarthy, Amy Stockwell, Toby M. Maher, Ann Millar, Philip L. Molyneaux, María Molina‐Molina, Vidya V. Navaratnam, Margaret Neighbors, Justin M. Oldham, Helen Parfrey, Gauri Saini, Ian Sayers, X Rebecca Sheng, Iain D. Stewart, Mary E. Strek, Martin D. Tobin, Moira K. B. Whyte, Maria Concetta Zarcone, Yingze Zhang, Fernando J. Martínez, Brian L. Yaspan, Carl Reynolds, David A. Schwartz, Carlos Flores, Imre Noth, Gisli R. Jenkins, Richard J. Allen, Louise V. Wain · 发表于：European Respiratory Journal · 年份：2026 · DOI：10.1183/13993003.00506-2026 · 被引用次数：11 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Lung Cancer Treatments and Mutations、Genetic Associations and Epidemiology

ABSTRACT Background Idiopathic pulmonary fibrosis (IPF) is a rare, incurable lung disease with a median survival of 3-5 years after diagnosis. Treatment options are limited. Genetic association studies can identify new genes involved in disease that might represent potential new drug targets, and it has been shown that drug targets with support from genetic studies are more likely to be successful in clinical development. Previous genome-wide association studies (GWAS) of IPF susceptibility have identified more than 20 signals implicating genes involved in multiple mechanisms, including telomere dysfunction, cell-cell adhesion, host defence immunity, various signalling pathways and, more recently, mitotic spindle assembly complex. Aim To leverage new datasets and genotype imputation to discover further genes involved in development of IPF that could yield new pathobiological avenues for exploration and to guide future drug target discovery. Methods We conducted a GWAS of IPF susceptibility including seven IPF case-control studies comprising 5,159 IPF cases and 27,459 controls of European ancestry, where IPF diagnosis was made by a respiratory clinician according to international guidelines. Genotypes were obtained from Whole Genome Sequencing (WGS) or from array-based imputation to the TOPMed WGS reference panel. New signals were replicated in independent biobanks with IPF defined using Electronic Healthcare Records. Bayesian fine-mapping was performed to identify the most li...