Mendelian randomization study of inflammatory proteins in causal relationship with heart failure
Objective To determine the causal relationship between 91 inflammatory proteins and heart failure by using two-sample Mendelian randomization analysis.Methods Data on 91 inflammatory proteins were collected from the GWAS database.Data on heart failure came from the FinnGens database.Inverse variance weighted,MR-Egger regression method,weighted median method and weighted mode were used to study the causal relationship between 91 inflammatory proteins and heart failure.Cochran's Q test,MR-PRESSO global test,funnel plot,leave-one-out method,and potential causal vari-able model were used for sensitivity analysis to verify the robustness,heterogeneity,and level pleiotropy of the results.Steiger test was used to determine whether there was a reverse causal relationship between heart failure and 91 inflammatory proteins.Results A total of 2 250 single nucleotide polymorphisms were obtained from 91 inflammatory proteins,and a total of six inflammatory proteins were identified as causal action.Inverse variance weighted analysis showed that matrix metallo-proteinase-1(OR=1.102,95％CI:1.043-1.165,P=0.001),tumor necrosis factor-β(OR=1.059,95％CI:1.018-1.103,P=0.005),T cell surface glycoprotein CD6 subtype(OR=1.067,95％CI:1.012-1.124,P=0.016),C-X-C motif chemokine 10(OR=1.060,95％CI:1.005-1.118,P=0.034)was positively correlated with heart failure;8 and Notch like epidermal growth factor related receptors(OR=0.941,95％CI:0.895-0.991,P=0.020),and monocyte chemoattractant protein 2(OR=0.903,95％CI:0.817-0.998,P=0.045)were negatively correlated with heart failure.There was no reverse causal rela-tionship between heart failure and inflammatory proteins by Steiger test.Sensitivity analysis results showed that there was no horizontal pleiotropy and significant heterogeneity among the selected single nucleotide polymorphisms,suggesting the robustness of the results.Conclusion There is a potential causal relationship between inflammatory proteins and the risk of heart failure,and no reverse causal association is found.
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