Mendelian randomization study on the causal relationship between body mass index and deep vein thrombosis

Objective To investigate the causal association between body mass index (BMI) and deep vein thrombosis (DVT) by using Mendelian randomization (MR) data with genome-wide association analysis (GWAS). Methods MR research method with genetic instrumental variables was used to explore the causal association between BMI and DVT in this study. Using the genetic data published in the GIANT database as a reference, a statistically significant single nucleotide polymorphism (SNP) was selected as a tool variable according to the MR-base platform (parameter P<5×10-8. Linkage disequilibrium r2<0.1). The causal association between BMI and DVT was determined by inverse variance weighted analysis (IVW), weighted median method and MR-Egger method, respectively. Further forest map of SNP-related BMI and DVT risk and scatter plots were drawn. Results A total of 79 SNPs related to birth weight were screened. IVW analysis showed OR=1.010, 95% CI:1.006-1.013, P=1.54×10-9. Weighted median method showed OR=1.011, 95% CI:1.005-1.016, P=1.34×10-4. MR-Egger method showed OR=1.014, 95%CI:1.007-1.022, P=4.58×10-4. The forest map showed that IVW, weighted median method, and MR-Egger regression all illustrated a significant causal association between BMI and DVT. MR-Egger showed that genetic pleiotropy did not bias the results (intercept=-0.00014, P=0.198). The scatter plot showed that the causal correlation estimated by the IVW method, the MR-Egger method and the weighted median method were similar, based on the slope of the line. Conclusion The results of two-sample Mendelian randomized analysis showed that there was a positive causal relationship between the risk of DVT and BMI, which was that the risk of DVT would increase by 1% corresponding to each elevation of BMI by its standard deviation. Key words: Body mass index; Deep venous thrombosis; Mendelian randomization study