Causal Association between Body Mass Index and Adverse Blood Transfusion Reactions: A Mendelian Randomization Study

The study aims to investigate the potential causative relationship between body mass index (BMI) and adverse blood transfusion reactions (ABTR). A two-sample Mendelian randomization (MR) study was conducted using inverse variance weighted (IVW), MR-Egger regression, weighted median method (WME), weighted model method (WM), simple model method, and simple median method. We utilized publicly available summary statistics from genome-wide association studies (GWAS) on BMI as the exposure (n = 126 003; GWAS ID: ebi-a-GCST90095042) and a GWAS for adverse blood transfusion reactions as the outcome variable (n = 199 451; GWAS ID: finn-b-ST19). We identified 42 single nucleotide polymorphisms of genome-wide significance in genome-wide association studies on BMI, which could serve as instrumental variables. The IVW technique showed that there is a causal relationship between BMI and negative blood transfusion outcomes (odds ratio (OR) = 0.29, 95% confidence interval (CI) = 0.10–0.85). Nonetheless, the effect value β of MR-Egger regression approach differed from that of IVW. A meta-analysis was conducted to determine the aggregated value of OR and 95% CI. The combined odds ratio (95% CI) was 0.43 (0.21–0.86), with a P-value of 0.017. Both the Cochran’s Q test and the funnel plot indicated no signs of heterogeneity or asymmetry, indicating the absence of directional pleiotropy. The results suggest that there may be a direct connection between BMI and ABTR.