Mediators of the association between allergic diseases and bronchiectasis: A bi-directional univariable and multivariable Mendelian randomization study and mediation analysis

• DOI: 10.1016/j.waojou.2025.101038
• Publication Date: 2025-03-12T10:04:37Z
• Authors: Ping-An Zhang; Jie-Lin Wang; Shi-Yan Fu; Hua-Lian Luo; Run-Dong Qin; Jing Li
• Keywords: Mendelian Randomization; Association (psychology)

BackgroundEmerging research indicates that bronchiectasis often coexists with a range of allergic illnesses. The pathogenesis both conditions is highly complex, involving variety interconnected factors, such as immune responses, metabolic pathways, and gut microbiota. However, the precise causal relationship between allergy-related remains poorly understood.Materials methodsWe obtained published GWAS datasets for 5 disorders (allergic asthma, rhinitis, atopic conjunctivitis, dermatitis, chronic rhinosinusitis) bronchiectasis, along data on 731 cells, 91 inflammatory proteins, 1400 plasma metabolites, 473 microbiotas. Using bi-directional two-sample Mendelian Randomization (TSMR), we explored relationships diseases validated these findings in replication cohort. We also applied Linkage Disequilibrium Score Regression (LDSC) to assess genetic correlations conditions. Additionally, mediating effects microbiota were assessed through two-step TSMR multivariate MR analysis.ResultsOur study revealed dermatitis all increased risk developing no identified reverse direction. positive associations observed respectively. total forty ninety nineteen species factors contributing onset. In mediation analysis, found ratio Retinol (Vitamin A) oleoyl-linoleoyl-glycerol (18:1 18:2) was factor asthma while level CD14 CD33dim HLA-DR + CD11b cells rhinitis. Two specific ratios—the Aspartate N-acetylglucosamine N-acetylgalactosamine Methionine phosphate ratio—served as, respectively, protective dermatitis-developing bronchiectasis.ConclusionOur suggest increase evidence relationship. Specifically, 3 ratios mediators bronchiectasis. Further studies are needed clarify underlying mechanisms.