Causal relationship between sphingosine-1-phosphate and acute respiratory distress syndrome based on two-sample bidirectional multivariable Mendelian randomization analysis
Liu Jinming
Cui Xudong
Tian Hongjun
Abstract：Objective To investigate the causal relationship between sphingosine-1-phosphate(S1P)and acute respiratory distress syndrome(ARDS)by two sample bidirectional multivariable Mendelian randomization(MR).Methods The data were summarized by genome-wide association studies(GWAS)sample database,S1P was used as exposure factor,ARDS was used as outcome factor,genetic loci associated with S1P were selected as tool variables,and two-sample bidirectional multivariable MR analysis was performed by using inverse-variance weighted(IVW)method,MR-Egger regression and weighted median estimator(WME)to evaluate the causal relationship between S1P and ARDS with OR.Results IVW results showed that S1P was associated with ARDS,S1P was a protective factor for ARDS(OR=0.492,95％CI 0.284-0.851),and WME results were similar(OR=0.431,95％CI 0.204-0.909),which also indicated that there was a causal relationship between the two.At the same time,sensitivity analysis results showed MR-Egger intercept analysis results,single nucleotide polymorphism(SNP)had no horizontal pleiotropy(P=0.33).Cochran's Q test showed that IVW(P=0.98＞0.05)and MR-Egger regression(P=0.99)did not have heterogeneity,which indicated that the obtained results were less likely to be affected by potential bias and the results were reliable.The results of multivariate positive MR analysis showed that age,BMI,smoking and drinking alcohol can increase the incidence of ARDS;Multivariate reverse MR analysis showed that ARDS increased the BMI of patients,and there is no causal relationship of the incidence of ARDS with age,smoking or alcohol consumption.Conclusions There is a negative causal relationship between S1P and ARDS,S1P is a protectivefctor for ARDS.
Keywords：Acute respiratory distress syndrome(ARDS)Mendelian randomization(MR)Sphingosine-1-phosphate(S1P)Causality
Publication Date：2025-05-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 414-419 )