Abstract: Objective The relationship between central obesity and hepatocellular carcinoma (HCC) is not completely clear. This study aimed to explore the potential causal associations between central obesity and HCC using Mendelian randomization analysis. Methods Two-sample Mendelian randomization analysis was conducted on the collected data in this study. Genome wide association study (GWAS) data with waist circumference, waist circumference adjusted by body mass index (WCadjBMI), hip circumference, hip circumference adjusted by BMI (HCadjBMI), waist-to-hip ratio and waist-to-hip ratio adjusted by BMI (WHRadjBMI) were obtained from a large-scale database containing 224,459 samples. The visceral fat volume dataset was derived from a European database which included information of 9,275,407 single nucleotide polymorphism (SNP) sites in 32,860 European subjects. The data set for HCC was drawn from the UK Biobank (UKB) database and included aggregated data from 372,184 European subjects. Results Inverse variance weighting (IVW) analysis showed that WCadjBMI increased the risk of HCC (OR=1.001, 95%CI (1.000, 1.001), P=0.024). This was confirmed by weighted median (WM) analysis (OR=1.001, 95%CI (1.000, 1.002), P=0.020), but not by MR-Egger regression analysis (OR=1.002, 95%CI (0.999, 1.004), P=0.135). Other indicators of central obesity were not associated with HCC. Conclusion There exists difference in the abilities of different central obesity indicators to impact on HCC. WCadjBMI may contribute to HCC development, suggesting that in a relatively thin population, central obesity is associated with HCC development with a causal relationship.

Key words: Central obesity, Hepatocellular carcinoma, Mendelian randomization