Autoimmune diseases and their genetic link to bronchiectasis: insights from a genetic correlation and Mendelian randomization study

Yue Su; Youqian Zhang; Yanhua Chai; Jinfu Xu

doi:10.3389/fimmu.2024.1343480

Autoimmune diseases and their genetic link to bronchiectasis: insights from a genetic correlation and Mendelian randomization study

Front Immunol. 2024 Apr 10:15:1343480. doi: 10.3389/fimmu.2024.1343480. eCollection 2024.

Authors

Yue Su^#¹, Youqian Zhang^#², Yanhua Chai^#¹, Jinfu Xu¹

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
² Health Science Center, Yangtze University, Jingzhou, Hubei, China.

^# Contributed equally.

Abstract

Background: Previous studies have demonstrated that autoimmune diseases are closely associated with bronchiectasis (BE). However, the causal effects between autoimmune diseases and BE remain elusive.

Methods: All summary-level data were obtained from large-scale Genome-Wide Association Studies (GWAS). The univariate Mendelian randomization (UVMR) was utilized to investigate the genetic causal correlation (r_g) of 12 autoimmune diseases and bronchiectasis, The Multivariable Mendelian Randomization (MVMR) method was used to explore the effects of the confounding factors. Further investigation was conducted to identify potential intermediate factors using mediation analysis. Finally, the linkage disequilibrium score regression (LDSC) method was used to identify genetic correlations among complex traits. A series of sensitivity analyses was performed to validate the robustness of the results.

Results: The LDSC analysis revealed significant genetic correlations between BE and Crohn's disease (CD) (r_g = 0.220, P = 0.037), rheumatoid arthritis (RA) (r_g = 0.210, P = 0.021), and ulcerative colitis (UC) (r_g = 0.247, P = 0.023). However, no genetic correlation was found with other autoimmune diseases (P > 0.05). The results of the primary IVW analysis suggested that for every SD increase in RA, there was a 10.3% increase in the incidence of BE (odds ratio [OR] = 1.103, 95% confidence interval [CI] 1.055-1.154, P = 1.75×10^-5, FDR = 5.25×10^-5). Furthermore, for every standard deviation (SD) increase in celiac disease (CeD), the incidence of BE reduced by 5.1% (OR = 0.949, 95% CI 0.902-0.999, P = 0.044, FDR = 0.044). We also observed suggestive evidence corresponding to a 3% increase in BE incidence with T1DM (OR = 1.033, 95% CI 1.001-1.066, P = 0.042, FDR = 0.063). Furthermore, MVMR analysis showed that RA was an independent risk factor for BE, whereas mediator MR analysis did not identify any mediating factors. The sensitivity analyses corroborated the robustness of these findings.

Conclusion: LDSC analysis revealed significant genetic correlations between several autoimmune diseases and BE, and further MVMR analysis showed that RA is an independent risk factor for BE.

Keywords: Crohn’s disease; Mendelian randomization; autoimmune diseases; bronchiectasis; rheumatoid arthritis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid / genetics
Autoimmune Diseases* / epidemiology
Autoimmune Diseases* / genetics
Bronchiectasis* / genetics
Genetic Predisposition to Disease*
Genome-Wide Association Study*
Humans
Linkage Disequilibrium
Mendelian Randomization Analysis*
Polymorphism, Single Nucleotide

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was sponsored by the National Natural Science Foundation of China (82330070, 81925001 to JX), the Innovation Program of Shanghai Municipal Education Commission (202101070007-E00097 to JX); the Program of Shanghai Municipal Science and Technology Commission (21DZ2201800 to JX). Shanghai Pujiang Program (22PJD065 to YS).