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

Huang, Qinyao; Guo, Jianglong; Zhao, Hongjun; Zheng, Yi; Zhang, Yuying

doi:10.1371/journal.pone.0292881

Cited by 2 publications

(1 citation statement)

References 58 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, the combined use of diverse MR analysis methods and multiple sensitivity analysis methods bolstered the reliability of the results. Additionally, musculoskeletal disorders are associated with various broadly defined cirrhosis [ 70 , 71 ] and diverse types of cancer [ 72 , 73 ]. To mitigate potential bias arising from these associations, the controls for liver cirrhosis and HCC in this study were defined to exclude broadly defined cirrhosis and all types of cancer, respectively, which ensured a higher degree of accuracy in the results of the causal analysis.…”

Section: Discussionmentioning

confidence: 99%

Genetic evidence of the causal relationship between chronic liver diseases and musculoskeletal disorders

Lu,

Li,

et al. 2024

J Transl Med

View full text Add to dashboard Cite

Background Chronic liver diseases constitute a major global public health burden, posing a substantial threat to patients’ daily lives and even survival due to the potential development of musculoskeletal disorders. Although the relationship between chronic liver diseases and musculoskeletal disorders has received extensive attention, their causal relationship has not been comprehensively and systematically investigated. Methods This study aimed to assess the causal relationships between viral hepatitis, primary biliary cholangitis, primary sclerosing cholangitis (PSC), liver cirrhosis, and hepatocellular carcinoma (HCC) with osteoporosis, osteoarthritis, and sarcopenia through bidirectional Mendelian randomization (MR) research. The traits related to osteoporosis and osteoarthritis included both overall and site-specific phenotypes, and the traits linked to sarcopenia involved indicators of muscle mass and function. Random-effect inverse-variance weighted (IVW), weighted median, MR-Egger, and Causal Analysis Using the Summary Effect Estimates were used to evaluate causal effects, with IVW being the main analysis method. To enhance robustness, sensitivity analyses were performed using Cochran’s Q test, MR-Egger intercept, MR-PRESSO global test, funnel plots, leave-one-out analyses, and latent causal variable model. Results The forward MR analysis indicated that PSC can reduce forearm bone mineral density (beta = − 0.0454, 95% CI − 0.0798 to − 0.0110; P = 0.0098) and increase the risk of overall osteoarthritis (OR = 1.012, 95% CI 1.002–1.022; P = 0.0247), while HCC can decrease grip strength (beta = − 0.0053, 95% CI − 0.008 to − 0.0025; P = 0.0002). The reverse MR analysis did not find significant causal effects of musculoskeletal disorders on chronic liver diseases. Additionally, no heterogeneity or pleiotropy was detected. Conclusions These findings corroborate the causal effects of PSC on osteoporosis and osteoarthritis, as well as the causal impact of HCC on sarcopenia. Thus, the implementation of comprehensive preventive measures is imperative for PSC and HCC patients to mitigate the risk of musculoskeletal disorders, ultimately improving their quality of life.

show abstract