Reverse Mendelian randomisation analysis of the causal effect of body mass index on cirrhosis risk: a large-scale genetic study

To investigate the potential causal effect of body mass index (BMI) on cirrhosis risk using a reverse Mendelian randomisation (MR) approach. We conducted a two-sample reverse MR study using summary statistics from genome-wide association studies (GWAS). The exposure data on cirrhosis were obtained from a GWAS of 1,564,786 participants, whereas the outcome data on BMI were derived from a GWAS of 67,832 individuals. Single-nucleotide polymorphisms (SNPs) significantly associated with cirrhosis were selected as instrumental variables. We performed various MR methods, including inverse variance weighted (IVW), MR-Egger, weighted median, simple mode and weighted mode, to estimate the causal effect. Sensitivity analyses were conducted to evaluate the robustness of our findings. Our analysis included 17 SNPs as instrumental variables. The primary IVW method (p = 0.586) and the MR-Egger method (0.344) showed a non-significant association between cirrhosis and BMI. Other MR methods yielded varying results, with effect estimates ranging from −0.007 to −0.068. Sensitivity analyses revealed non-significant heterogeneity (p = 0.012) and non-significant directional pleiotropy (MR-Egger intercept = 0.013, p = 0.426). This reverse MR study that analysed the causal relationship between liver cirrhosis and BMI found that the primary IVW analysis and MR-Egger results indicated no association between the two. The absence of horizontal pleiotropy and heterogeneity ensured the accuracy of the study’s conclusions.