Abstract

Non-alcoholic fatty liver disease (NAFLD) has been found to be associated with osteoporosis (OP) in observational studies. However, the precise causal relationship between NAFLD and OP remains unclear. Here, we used Mendelian randomization (MR) to explore the causal relationship. We selected NAFLD-related single-nucleotide polymorphisms from a genome-wide meta-analysis (8434 cases and 434,770 controls) as instrumental variants. We used inverse variance weighted analysis for the primary MR analysis. Furthermore, we used similar methodologies in parallel investigations of other chronic liver diseases (CLDs). We performed sensitivity analyses to ensure the reliability of the results. We observed a causality between NAFLD and forearm bone mineral density (FABMD) (beta-estimate [β]: − 0.212; p-value: 0.034). We also found that sclerostin can act as a mediator to influence the NAFLD and FABMD pathways to form a mediated MR network (mediated proportion = 8.8%). We also identified indications of causal relationships between other CLDs and OP. However, we were unable to establish any associated mediators. Notably, our analyses did not yield any evidence of pleiotropy. Our findings have implications in the development of preventive and interventional measures aimed at managing low bone mineral density in patients with NAFLD.

中文翻译：

---

孟德尔随机研究中硬化蛋白介导非酒精性脂肪肝对骨矿物质密度的影响

摘要

观察性研究发现非酒精性脂肪肝（NAFLD）与骨质疏松症（OP）相关。然而，NAFLD 和 OP 之间的确切因果关系仍不清楚。在这里，我们使用孟德尔随机化（MR）来探索因果关系。我们从全基因组荟萃分析（8434 例病例和 434,770 例对照）中选择了与 NAFLD 相关的单核苷酸多态性作为工具变异。我们使用逆方差加权分析进行主要 MR 分析。此外，我们在其他慢性肝病（CLD）的平行研究中使用了类似的方法。我们进行了敏感性分析以确保结果的可靠性。我们观察到 NAFLD 与前臂骨矿物质密度 (FABMD) 之间存在因果关系（β 估计值 [ β ]：− 0.212；p值：0.034）。我们还发现硬化蛋白可以作为介质影响 NAFLD 和 FABMD 通路，形成介导的 MR 网络（介导比例 = 8.8%）。我们还发现了其他 CLD 和 OP 之间因果关系的迹象。然而，我们无法建立任何相关的调解员。值得注意的是，我们的分析没有产生任何多效性的证据。我们的研究结果对于制定旨在管理 NAFLD 患者低骨密度的预防和干预措施具有重要意义。