Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study

作者：Aiyong Cui, Peilun Xiao, Zhiqiang Fan, Jinlai Lei, Shuang Han, Dan-Long Zhang, Xing Wei, Pengfei Wang, Yan Zhuang · 发表于：Frontiers in Endocrinology · 年份：2023 · DOI：10.3389/fendo.2023.1215790 · 被引用次数：27 · 研究领域：Liver Disease Diagnosis and Treatment、Genetic Associations and Epidemiology、Bone health and osteoporosis research

Introduction The causal association between non-alcoholic fatty liver disease (NAFLD) and osteoporosis remains controversial in previous epidemiological studies. We employed a bidirectional two-sample Mendelian analysis to explore the causal relationship between NAFLD and osteoporosis. Method The NAFLD instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Two-sample Mendelian randomization (MR) analyses were used to estimate the causal effect of NAFLD on osteoporosis, fracture, and fall. Reverse Mendelian randomization analysis was conducted to estimate the causal effect of osteoporosis on NAFLD. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic. The heterogeneity effect of IVs was detected by MR-Egger and IVW analyses. Results Five SNPs (rs2980854, rs429358, rs1040196, rs738409, and rs5764430) were chosen as IVs for NAFLD. In forward MR analysis, the IVW-random effect indicated the causal effect of NAFLD on osteoporosis (OR= 1.0021, 95% CI: 1.0006-1.0037, P = 0.007) but not on fracture (OR= 1.0016, 95% CI: 0.998-1.0053, P = 0.389) and fall (OR= 0.9912, 95% CI: 0.9412-1.0440, P = 0.740). Furthermore, the reverse Mendelian randomization did not support a causal effect of osteoporosis on NAFLD (OR= 1.0002, 95% CI: 0.9997-1.0007, P = 0.231). No horizontal pleiotropic was detected in all MR analyses. ...