Association between nonalcoholic fatty liver disease and bone mineral density: Mendelian randomization and mediation analysis
Abstract
Background Observational studies have reported significant association between non-alcoholic fatty liver disease (NAFLD) and bone mineral density (BMD), a critical indicator of bone health. We aimed to investigate whether NAFLD is a cause for changes in BMD. Methods We selected 29 independent SNPs as instrumental variables for NAFLD. A range of Mendelian randomization (MR) methods, namely the inverse variance-weighted (IVW) method, weighted-median, weighted-mode, and MR-Egger regression, were utilized to determine the causal effects of NAFLD on BMD. Two-step MR analysis was conducted to determine the mediating effect of fasting glucose, insulin, glycosylated hemoglobin, low-density cholesterol, and body-mass index on the association between NAFLD and BMD. False-discovery-rate (FDR) was used to correct for multiple testing bias. Results The IVW-method indicated a significantly inverse association between genetically predicted NAFLD and total body BMD (β = −0.04, 95 % CI -0.07 to −0.02, FDR = 0.010). Notably, the relationship was more pronounced in participants over 60 years of age (β = −0.06, 95 % CI -0.11 to −0.02, FDR = 0.030). Inverse associations were observed in other subpopulations and in site-specific BMD, though they were not statistically significant after correcting for multiple testing. We observed a significantly positive association between NAFLD and the risk of osteoporosis. Consistency in results was observed across multiple MR methods and in the repeated…
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