Autoimmune diseases and COPD risk: A Mendelian randomization study

Abstract

BackgroundStudies in epidemiology have indicated a link between chronic obstructive pulmonary disease (COPD) and various autoimmune conditions.This study aimed to investigate the potential causal link between nine autoimmune diseases with a genetic basis and COPD using a two-sample Mendelian randomization (MR) analysis. MethodTo test the impact of susceptibility to immune-related outcomes on genetic prediction of COPD risk, we used pooled statistics from the largest genome-wide association study (GWAS) in Europe in a two-sample MR setting.Genetic data for type 1 diabetes, hypothyroidism, systemic lupus erythematosus, and primary biliary cirrhosis were obtained from the European Bioinformatics Institute (EBI), while data for multiple sclerosis and primary sclerosing cholangitis were extracted from the Integrative Epidemiology Unit (IEU) database. Additionally, genetic data for ulcerative colitis, rheumatoid arthritis, and celiac disease were also collected.These nine autoimmune diseases and the COPD cohort from the UK Biobank (1605 cases and 461,328 controls) were analyzed separately as exposure and outcome.Our primary method for the initial screening was inverse variance weighting (IVW).The MR-Egger regression test assessed multivariate validity, while the Cochran’s Q test examined heterogeneity.To ensure the reliability of the findings, a leave-one-out analysis was conducted. ResultIVW discovered proof of type 1 diabetes (OR = 1.0003; 95 % CI = 1.0000–1.0005; P = 0.046), hypothyroidism (OR = 1.0004; 95 % CI = 1.0001–1.0008; P = 0.0263), celiac disease (OR = 1.0002; 95 % CI = 1.0000–1.0004; P = 0.0168) and systemic lupus erythematosus (OR = 1.0002; 95 % CI = 1.0000–1.0004; P = 0.049) were significantly linked to the heightened risk of COPD with no signs of variation or pleiotropy.Even after accounting for potential confounding factors like smoking, the correlation remained robust.Additionally, our research found that the IVW method did not indicate any causal link between COPD and multiple sclerosis, ulcerative colitis, rheumatoid arthritis, primary biliary cirrhosis, or primary sclerosing cholangitis (all P >0.05). ConclusionThis research discovered that individuals with type 1 diabetes, hypothyroidism, celiac disease, and systemic lupus erythematosus have a higher likelihood of developing COPD.Additionally, this research revealed no connection between COPD and multiple sclerosis, ulcerative colitis, rheumatoid arthritis, primary biliary cirrhosis, or primary sclerosing cholangitis.