The associations of alcoholic liver disease and nonalcoholic fatty liver disease with bone mineral density and the mediation of serum 25-Hydroxyvitamin D: A bidirectional and two-step Mendelian randomization

作者：Qinyao Huang, Jianglong Guo, Hongjun Zhao, Yi Zheng, Yuying Zhang · 发表于：PLoS ONE · 年份：2023 · DOI：10.1371/journal.pone.0292881 · 被引用次数：10 · 研究领域：Genetic Associations and Epidemiology、Liver Disease Diagnosis and Treatment、Bone health and osteoporosis research

BACKGROUND: Reduced bone mineral density (BMD) and osteoporosis are common in chronic liver diseases. However, the causal effect of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) on BMD remains uncertain. OBJECTIVES: This study uses a two-sample Mendelian randomization (MR) design to evaluate the genetically predicted effect of ALD and NAFLD on BMDs using summary data from publically available genome-wide association studies (GWASs). METHODS: The GWAS summary statistics of ALD (1416 cases and 213,592 controls) and NAFLD (894 cases and 217,898 controls) were obtained from the FinnGen consortium. BMDs of four sites (total body, n = 56,284; femoral neck, n = 32,735; lumbar spine, n = 28,498; forearm, n = 8143) were from the GEnetic Factors for OSteoporosis Consortium. Data for alcohol consumption (n = 112,117) and smoking (n = 33,299) and serum 25-Hydroxyvitamin D (25-OHD) level (n = 417,580) were from UK-biobank. We first performed univariate MR analysis with the Inverse Variance Weighted (IVW) method as the primary analysis to investigate the genetically predicted effect of ALD or NAFLD on BMD. Then, multivariate MR and mediation analysis were performed to identify whether the effect was mediated by alcohol consumption, smoking, or serum 25-OHD level. RESULTS: The MR results suggested a robust genetically predicted effect of ALD on reduced BMD in the femoral neck (FN-BMD) (IVW beta = -0.0288; 95% CI: -0.0488, -0.00871; P = 0.00494) but not the othe...