Associations between body circumference and testosterone levels and risk of metabolic dysfunction-associated fatty liver disease: A Mendelian randomization study

BACKGROUD: Body circumference and testosterone levels has been reported as associated with metabolic dysfunction-associated fatty liver disease (MAFLD) risk. However, whether body circumference and testosterone levels play a role in the development of MAFLD remains inconclusive. METHODS: Using a large database of genome-wide association studies, genetic loci that are independent of each other and strongly associated with body circumference and testosterone levels were selected as instrumental variables, the causal relationship between body circumference and testosterone and risk of MAFLD was investigated by two-sample Mendelian randomization methods such as inverse variance weighted (IVW), MR-Egger regression, and weighted median estimator (WME), using the odds ratios (ORs) as evaluation indicators. RESULTS: A total of 377 SNPs were included as instrumental variables in this study, including 3 for neck circumference, 165 for waist circumference, 78 for hip circumference, and 131 for testosterone levels. Using the two-sample Mendelian randomization method described above to derive a causal association between exposure and outcome, the IVW method was used as the primary method of analysis, and the results of the analysis showed a causal association between all four exposure factors and MAFLD, with an OR of neck circumference was 0.87,95%CI:0.78~0.98, P =0.018; and an OR of waist circumference of 2.88, 95%CI: 1.73 to 4.81, P <0.001, OR of hip circumference was 0.48, 95%CI:0.24~0.96, P =0.039, and an OR of testosterone level of 1.75, 95%CI:1.17~2.62, P =0.006. Cochran Q test by IVW and MR-Egger method showed that SNPs did not have intergenic heterogeneity, and the test for pleiotropy indicated a weak possibility of pleiotropy in the causal analysis. CONCLUSION: The results of the two-sample Mendelian randomization analysis showed that waist circumference and testosterone level were risk factors for MAFLD, and the incidence of MAFLD increased as both increased; neck circumference and hip circumference were protective factors for MAFLD, and the risk of MAFLD decreased as both increased.