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

Abstract

Backgroud Body circumference and testosterone levels have 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 344 SNPs were included as instrumental variables in this study, including 180 for waist circumference, 29 for waist-to-hip ratio, and 135 for testosterone levels. Using the above two-sample Mendelian Randomization method to derive the causal association between exposure and outcome. The results of this study showed that three exposure factors were causally associated with the risk of MAFLD. Waist circumference obtained three statistically significant results for IVW, WME and Weighted mode (IVW: OR = 3.53, 95%CI: 2.23–5.57, P < 0.001; WME: OR = 3.88, 95%CI: 1.81–8.29, P < 0.001; Weighted mode: OR = 3.58, 95%CI: 1.05–12.16, P = 0.043). Waist-to-hip ratio obtained one statistically significant result for IVW (OR = 2.29, 95%CI: 1.12–4.66, P = 0.022). Testosterone levels obtained one statistically significant result for IVW (OR = 1.93, 95%CI: 1.30–2.87, P = 0.001). Waist circumference, waist-to-hip ratio and testosterone level were considered as risk factors for MAFLD. The Cochran Q test for IVW and MR-Egger method indicated that there was no intergenic heterogeneity in SNPs. The test for pleiotropy indicated that the possibility of pleiotropy in the causal analysis was weak. Conclusion The results of the two-sample Mendelian randomization analysis showed that waist circumference was the exact risk factor for MAFLD, waist-to-hip ratio and testosterone levels were potential risk factors for MAFLD, the risk of developing MAFLD increases with these three exposure factors.

Investigating the causal associations between five anthropometric indicators and nonalcoholic fatty liver disease: Mendelian randomization study

“…Consequently, some studies support visceral obesity with WC and BF as primary measures of a crucial risk factor for NAFLD[ 44 ]. Based on European GWAS pooled data, a previous study reported partially different findings compared with our findings, indicating that WHR may be a potential risk factor for NAFLD[ 45 ]. Several factors could explain this difference.…”

“…Although previous studies have extensively investigated the relationship between AO and NAFLD, there are limited studies on the association between other anthropometric measures[ 45 , 46 ]. This study expands and validates these results by incorporating a wider range of anthropometric measures, offering additional supporting evidence for a causal association in early-stage NAFLD.…”

Analysis of risk factors for fatty liver disease in children with Wilson’s disease

“…Owing to decreasing estrogen levels in postmenopausal females, the loss of estrogen-based protection may be the reason for the increased NAFLD risk in these females [ 23 ]. Additionally, testosterone levels in men are considered a potential risk factor for FLD [ 24 ]. No difference was observed in children regarding the risk of Wilson’s disease complicated with FLD based on gender; this related to the fact that children are not sexually mature.…”

Plasma lipids, alcohol intake frequency and risk of Osteoarthritis: a Mendelian randomization study

“…In this study, plasma lipids (TC, TG, HDL, LDL) and alcohol intake frequency were used as exposure factors, and single nucleotide polymorphisms (SNPs) loci significantly associated with the above exposure factors were selected as instrumental variables(IVs), and the outcome variable was OA, and the causal association analysis between exposure and outcome was performed using a two-sample MR analysis approach based on a publicly available genome wide association study (GWAS) database of large samples, and Cochran Q test to assess heterogeneity, and finally sensitivity analysis to verify the reliability of the causal association results. MR analysis needs to satisfy the following three core hypotheses: ①there is a strong association between instrumental variable Z and exposure factor X [ 17 ]; ②instrumental variable Z is not associated with any confounding factor U of the exposure-outcome association; and ③the instrumental variable Z does not affect the outcome Y, except possibly by association with the exposure X [ 18 ]. The two-sample MR study model is shown in Fig.…”