Genetic causal association between malnutrition, overweight and venous thromboembolism: a two-sample Mendelian randomisation study

Despite previous observational studies suggesting that malnutrition could be involved in venous thromboembolism (VTE), definitive causality still lacks high-quality research evidence. This study aims to explore the genetic causal association between malnutrition and VTE. The study was performed using summary statistics from genome-wide association studies for VTE (cases = 23 367; controls = 430 366). SNP associated with exposure was selected based on quality control steps. The primary analysis employed the inverse variance weighted (IVW) method, with additional support from Mendelian randomisation (MR)-Egger, weighted median and weighted mode approaches. MR-Egger, leave-one-SNP-out analysis and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for sensitivity analysis. Cochran's Q test was used to assess heterogeneity between instrumental variables (IV). IVW suggested that overweight has a positive genetic causal effect on VTE (OR = 1·1344, 95 % CI = 1·056, 1·2186, <i>P</i> < 0·001). No genetic causal effect of malnutrition (IVW: OR = 0·9983, 95 % CI = 0·9593, 1·0388, <i>P</i> = 0·9333) was found on VTE. Cochran's Q test suggests no possible heterogeneity in both related exposures. The results of the MR-Egger regression suggest that the analysis is not affected by horizontal pleiotropy. The results of the MR-PRESSO suggest that there are no outliers. The results revealed a statistical genetic association where overweight correlates with an increased risk of VTE. Meanwhile, no genetic causal link was observed between malnutrition and VTE. Further research is warranted to deepen our understanding of these associations.