基于孟德尔随机化的血液代谢物与血栓闭塞性脉管炎因果关系分析OA

Objective To explore the causal asssociation between blood metabolites and thromboangiitis obliterans(TAO)by employing Mendelian randomization(MR)analysis.Methods Genome-Wide Association Study database was used to collect blood metabolite data from 8 299 Europeans and whole-genome association data from 114 patients with TAO and 381 977 controls.Using 1 091 blood metabolites and 309 metabolite ratios as exposure factors and TAO as the outcome,causal analyses were conducted using inverse variance weighting,MR-Egger regression,weighted median,and weighted mode methods.Sensitivity analyses were conducted using the MR-Egger intercept test,Cochrane Q test,MR-PRESSO,and leave-one-out analysis so as to enhance the robustness of results.Metabolic pathway analysis of metabolites was carried out using the Metabo Analyst platform.Results Fifty-two blood metabolites were identified to be causally associated with TAO.Of these,22 metabolites,including N2,N2-dimethylguanosine,were risk factors for TAO,while 30 metabolites,including tetradecanodienate(14∶2),were protective factors of TAO.Sensitivity analyses supported the robustness and reliability of these causal associations.Metabolic pathway analysis showed that two pathways,folic acid-mediated one-carbon unit metabolism,and glycine-serine-threonine metabolism,were associated with TAO.Conclusion Fifty-two blood metabolites showed causal associations with TAO risk.Two metabolic pathways may be involved in TAO pathogenesis,providing potential targets for diagnosis and treatment of TAO and informing its screening and mechanistic studies.