Mendelian randomization analysis of the causal relationship between plasma proteins and childhood asthma.

Abstract

Existing studies have suggested a significant association between plasma proteins and childhood asthma, but the specific causal relationship between them remains unclear. Therefore, we aimed to evaluate the causal relationship between plasma proteins and childhood asthma using Mendelian randomization (MR) methods. We conducted a 2-sample MR analysis and a reverse MR analysis. The GWAS summary statistics for plasma proteins were derived from a European population, covering a total of 4907 plasma proteins. The GWAS summary statistics for childhood asthma were obtained from the FinnGen database, including 3025 childhood asthma patients and 135,449 normal controls. Five MR methods, which include inverse-variance weighted, weighted median, MR-Egger, weighted mode, and simple mode, were utilized to investigate the causal relationship between plasma proteins and childhood asthma. The results indicated that ITIH4 is a risk factor for childhood asthma, while THSD1, AMIGO2, L1CAM, MICB, and SELE are protective factors. Leave-one-out analysis, heterogeneity tests, and pleiotropy tests confirmed the reliability and robustness of our findings. Additionally, reverse MR analysis showed no significant causal relationship between childhood asthma and ITIH4, THSD1, AMIGO2, L1CAM, MICB, and SELE. Our study used MR methods to confirm the specific causal relationships between 4907 plasma proteins and childhood asthma. Specifically, ITIH4 was likely to be significantly associated with an increased risk of childhood asthma, while THSD1, AMIGO2, L1CAM, MICB, and SELE were likely to be significantly associated with a reduced risk of childhood asthma.