Effect of muscle strength on deep vein thrombosis: A Mendelian randomization study

Abstract

Deep vein thrombosis (DVT) is a serious condition characterized by blood clots in deep veins, posing a significant public health burden. Muscle strength has been implicated as a potential risk factor for DVT due to its influence on venous return. This study aims to investigate the causal association between muscle strength and DVT using a Mendelian randomization (MR) approach, leveraging genetic variants as instrumental variables (IVs). We conducted a 2-sample MR analysis using genome-wide association study (GWAS) data for hand-grip strength and DVT. IVs were selected based on their significant associations with muscle strength and DVT, as well as their linkage disequilibrium patterns. We employed statistical methods including inverse-variance weighting (IVW), MR-Egger, and weighted median to address pleiotropy bias. Sensitivity analyses were conducted to evaluate the robustness of the results. A total of 21 and 14 independent IVs were identified for hand grip strength (EWGSOP) and hand grip strength (FNIH), respectively. IVW analysis revealed a consistent causal and negative association between both definitions of hand grip strength and DVT (EWGSOP: OR = 0.702, 95% CI: 0.511-0.964, P = .029; FNIH: OR = 0.715, 95% CI: 0.570-0.898, P = .004). No directional pleiotropy was detected in MR-Egger and MR-PRESSO analyses for either definition (EWGSOP: MR-Egger Intercept P = .516; MR-PRESSO global test P = .162; FNIH: MR-Egger Intercept P = .569; MR-PRESSO global test P = .371).Sensitivity analyses demonstrated the stability of the causal effect estimates, with little influence from individual IVs. The MR analysis provided evidence of a causal association between muscle strength and DVT risk, suggesting that increasing muscle strength may have a protective effect. These findings have implications for preventive strategies and the promotion of resistance exercises and muscle-strengthening activities. Further research and validation of these results could inform clinical guidelines and interventions for DVT prevention.

Figure 1.

Diagram for key assumptions of MR analyses. DVT = deep vein thrombosis, HGS = hand grip strength, IVs = instrumental variables, MR = Mendelian randomization, SNPs = single nucleotide polymorphisms.

Figure 2.

Scatter plots of causality. The slope of each line corresponds to the estimated MR effect in different models. (A) Hand grip strength (EWGSOP; ebi-a-GCST90007526); (B) hand grip strength (FNIH; ebi-a-GCST90007529). MR = Mendelian randomization.

Figure 3.

Forest plot for individual causal effect estimate. (A) Hand grip strength (EWGSOP; ebi-a-GCST90007526); (B) Hand grip strength (FNIH; ebi-a-GCST90007529).