■观察性研究报告了非酒精性脂肪性肝病(NAFLD)和骨密度(BMD)之间的显著关联,骨骼健康的关键指标。我们的目的是调查NAFLD是否是BMD变化的原因。
■我们选择了29个独立的SNP作为NAFLD的工具变量。一系列孟德尔随机化(MR)方法,即逆方差加权(IVW)方法,加权中位数,加权模式,和MR-Egger回归,用于确定NAFLD对BMD的因果影响。进行两步MR分析以确定空腹血糖的中介作用,胰岛素,糖化血红蛋白,低密度胆固醇,和体重指数对NAFLD和BMD之间的关联。错误发现率(FDR)用于校正多重测试偏差。
■IVW方法表明遗传预测的NAFLD与总体BMD之间存在显着负相关(β=-0.04,95%CI-0.07至-0.02,FDR=0.010)。值得注意的是,这种关系在60岁以上的参与者中更为明显(β=-0.06,95%CI-0.11~-0.02,FDR=0.030).在其他亚群和特定部位BMD中观察到反向关联,尽管经过多次测试校正后,它们没有统计学意义。我们观察到NAFLD与骨质疏松症风险之间存在显著正相关。在多种MR方法和重复分析中观察到结果的一致性。空腹血糖,胰岛素,糖化血红蛋白介导25.4%(95%CI17.6-31.5%),18.9%(12.0-24.9%),和27.9%(19.9-36.7%)的NAFLD对BMD的影响,分别。
■我们的发现强调了NAFLD和BMD之间可能存在的因果关系。表明NAFLD可能会对骨骼健康产生不利影响,尤其是老年人。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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 analysis. Fasting glucose, insulin, and glycosylated hemoglobin mediated 25.4 % (95 % CI 17.6-31.5 %), 18.9 % (12.0-24.9 %), and 27.9 % (19.9-36.7 %) of the effect of NAFLD on BMD, respectively.
UNASSIGNED: Our findings underscore a probable causal negative link between NAFLD and BMD, indicating that NAFLD might detrimentally affect bone health, especially in older individuals.