Objective To analyze the causal relation between cystatin C level and deep vein thrombosis (DVT) based on bidirectional Mendelian randomization (MR). Methods The genome⁃wide association study dataset of cystatin C and DVT was obtained from IEU OpenGWAS Project. Cystatin C and DVT were mutually used as exposure factors and outcomes, and single nucleotide polymorphism (SNP) significantly related to exposure factors and outcomes were used as instrumental variables. A bidirectional MR analysis was performed using five methods as follows: inverse variance weighted (IVW), MR⁃Egger test, weighted median method, simple mode method and weighted mode. The Cochran's Q test was adopted to evaluate the heterogeneity of instrumental variables, and the MR⁃Egger intercept was employed to evaluate horizontal pleiotropy. The leave⁃one⁃out method was used to verify the influence of single SNP on the results. Results The results of forward MR revealed that cystatin C level had a positive causal association with the occurrence risk of DVT (OR=1.004, P<0.05). Similar causal relation was obtained by simple mode method and weighted mode (OR>1, P<0.05). The reverse MR results indicated that there was no dominant negative causal relation between DVT and cystatin C level (OR=0.485, P>0.05), and the similar causal relation was also obtained by MR⁃Egger, simple mode method and weighted mode (OR>1, P>0.05). There was no significant heterogeneity of instrumental variables in the forward MR analysis, whereas there was significant heterogeneity of instrumental variables in the reverse MR analysis, but there was no horizontal pleiotropy in both MR analyses. In analysis of forward MR leave⁃one⁃out method, the overall influence of cystatin C on DVT was not significantly changed after removing single SNP one by one. Conclusion There may be a causal relation between cystatin C level and DVT, but the causal relation of DVT on cystatin C level is uncertain.  

无