Analysis of causal relationship between irritable bowel syndrome and osteoporosis

ZHANG Zhisheng; DENG Xinyi; AI Zisheng; LIU Yue; YANG Tieyi

doi:10.3969/j.issn.1002-266X.2025.04.019

Abstract：Objective To analyse the causal relationship between irritable bowel syndrome(IBS)and osteoporosis(OP)and to provide a genetic perspective for the prevention of OP.Methods The datasets of IBS and OP were obtained from the genome-wide association studies(GWAS)public database,and two-way Mendelian randomisation(MR)analyses were used to explore the causal relationship between IBS and OP from forward and reverse directions,respectively.For-ward MR analysis used single-nucleotide polymorphisms(SNPs)associated with IBS as instrumental variables,IBS as ex-posure factor and OP as outcome variable;the reverse MR analysis used SNPs associated with OP as instrumental vari-ables,OP as exposure factor and IBS as outcome variable.Inverse variance weighted(IVW)analysis was used as the pri-mary MR analysis method,supplemented by weighted median(WM),MR-Egger regression,simple and weighted models to assess the causal relationship between IBS and OP.The MR-Egger intercept method was employed to assess the horizon-tal multiplicity of instrumental variables,Cochrane's Q test was utilized to assess the heterogeneity of the instrumental vari-ables,funnel plot symmetry was used to observe the potential publication bias,and leave-one-out method was used to as-sess the sensitivity of individual SNP to causal effects.Results Fifty-six SNPs were included as instrumental variables in the forward MR analysis;IVW analysis showed a positive causal association between IBS and OP(OR=1.002 8,95%CI:1.000 7-1.004 8,P=0.007 3);WM,simple mode method and weighted mode method analyses were in the same direc-tion as the IVW analysis results;MR-Egger intercept method,Cochrane's Q test,funnel plot and leave-one-out analysis all showed reliable results.A total of 50 SNPs were included as instrumental variables in the reverse MR analyses;IVW analyses showed that there was no reverse causality between IBS and OP(OR=2.838 5,95%CI:0.546 4-14.747 0,P=0.214 6);MR-Egger regression method,WM,simple model method,and weighted model method analyses all found no reverse causality(all P>0.05);MR-Egger intercept method,funnel plot,and leave-one-out analyses showed reliable analyses,and Cochrane's Q test suggested heterogeneity among the included SNPs,but did not affect the robustness of causal inference.Conclusion IBS was significantly and causally associated with an increased risk of developing OP,whereas OP was not significantly and causally associated with an increased risk of developing IBS.