Shared genetic etiology between idiopathic pulmonary fibrosis and COVID-19 severity

作者：João P. S. Fadista, Luke M. Kraven, Juha S. Karjalainen, Shea J. Andrews, Frank Geller, John Kenneth Baillie, Louise V. Wain, Gisli R. Jenkins, Bjarke Feenstra · 发表于：EBioMedicine · 年份：2021 · DOI：10.1016/j.ebiom.2021.103277 · 被引用次数：97 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Long-Term Effects of COVID-19、Inflammatory Myopathies and Dermatomyositis

Background Idiopathic pulmonary fibrosis (IPF) is a complex lung disease, characterized by progressive lung scarring. Severe COVID-19 is associated with substantial pneumonitis and has a number of shared major risk factors with IPF. This study aimed to determine the genetic correlation between IPF and severe COVID-19 and assess a potential causal role of genetically increased risk of IPF on COVID-19 severity. Methods The genetic correlation between IPF and COVID-19 severity was estimated with linkage disequilibrium (LD) score regression. We performed a Mendelian randomization (MR) study for IPF causality in COVID-19. Genetic variants associated with IPF susceptibility ( P <5 × 10 −8 ) in previous genome-wide association studies (GWAS) were used as instrumental variables (IVs). Effect estimates of those IVs on COVID-19 severity were gathered from the GWAS meta-analysis by the COVID-19 Host Genetics Initiative (4,336 cases & 623,902 controls). Findings We detected a positive genetic correlation of IPF with COVID-19 severity (rg=0·31 [95% CI 0·04–0·57], P = 0·023). The MR estimates for severe COVID-19 did not reveal any genetic association (OR 1·05, [95% CI 0·92–1·20], P = 0·43). However, outlier analysis revealed that the IPF risk allele rs35705950 at MUC5B had a different effect compared with the other variants. When rs35705950 was excluded, MR results provided evidence that genetically increased risk of IPF has a causal effect on COVID-19 severity (OR 1·21, [95% CI 1·06–1·38]...