Effects of nonalcoholic fatty liver disease on sarcopenia: evidence from genetic methods.

With the aging of the population, sarcopenia has become more common. Studies have shown a broad association between liver disease and sarcopenia. However, this link remains unclear. Our study explored the link between NAFLD and sarcopenia and predicting the pathogenesis. To begin, we investigated the causal relationship and genetic correlation between them using MR and LDSC. Second, each GWAS was annotated by MAGMA. The annotated genes were analyzed for pleiotropy using the PLACO approach. Finally, functional analysis was conducted on the identified pleiotropic genes. We observed a significant genetic correlation between NAFLD and sarcopenia. Subsequently, we conducted gene-level pleiotropy analysis using PLACO and identified a total of 153 genes with pleiotropic effects. Functional analysis revealed enrichment of these genes in various tissues, including pancreas, liver, heart, blood, brain, and muscle, with involvement in cellular regulation, intracellular function, and antigen response. Moreover, our MR analysis provided evidence of a causal relationship between NAFLD and sarcopenia. Our study has discovered the genetic and causal relationships between NAFLD and sarcopenia, providing further insights into their pathophysiological mechanisms. The identification of pleiotropic genes also offers potential targets for future drug therapies aimed at controlling or treating NAFLD and sarcopenia.

Causal Effects of Genetically Predicted Cystatin C on Osteoporosis: A Two-Sample Mendelian Randomization Study.

Objectives: Although it has long been reported that high levels of cystatin C could contribute to the development of osteoporosis in some studies, no evidence has established a causal association between them thus far. Methods: A Mendelian randomization (MR) study was conducted to determine the causal effect of cystatin C on osteoporosis based on public databases obtained from separately published genome-wide association studies (GWASs). The single-nucleotide polymorphisms (SNPs) for cystatin C were extracted from the MR-Base (CKDGen, 33,152 participants), and the SNPs for osteoporosis were extracted from the United Kingdom Biobank project (United Kingdom Biobank, including 5,266 osteoporosis cases and 331,893 controls). We defined the odds ratio (OR) of IVW methods as the primary outcome. In addition, weighted median and MR-Egger regressions were used in the sensitivity analysis. Results: In IVW, we found that genetically predicted cystatin C was causally associated with the risk of osteoporosis with an OR of 1.02 [95% confidence interval (CI) = 1.003-1.025, p = 0.01]. In the further sensitivity analysis, weighted median regression also showed directionally similar estimates (OR = 1.02, 95% CI = 1.005-1.03, p = 0.005), and MR-Egger regression (OR = 1.02, 95% CI = 1.000-1.036, p = 0.15) revealed similar estimates but with lower precision. The funnel plot, MR-Egger intercept, and MR-PRESSO all indicate that no directional pleiotropic effect was observed. Conclusion: In conclusion, our MR study showed evidence of a causal association between serum cystatin C levels and osteoporosis, which also needs to be verified by studies with larger sample sizes in the future. Early monitoring of cystatin C may enable us to prevent osteoporosis-related diseases.

Prognostic value of neutrophil/lymphocyte, platelet/lymphocyte, lymphocyte/monocyte ratios and Glasgow prognostic score in osteosarcoma: A meta-analysis.

BACKGROUND: Some studies investigated the prognostic role of several blood biomarkers, including the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR) and Glasgow prognostic score (GPS), in osteosarcoma, but their results were inconsistent with each other. AIM: To identify the prognostic value of NLR, PLR, LMR and GPS in osteosarcoma patients through reviewing relevant studies. METHODS: The PubMed, EMBASE, Web of Science and CNKI databases were searched up to October 2, 2021. The primary and second outcomes were overall survival (OS) and disease-free survival (DFS), respectively. The hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the association between these indicators and prognosis of osteosarcoma patients. RESULTS: A total of 13 studies involving 2087 patients were eventually included. The pooled results demonstrated that higher NLR and GPS were significantly associated with poorer OS (HR = 1.88, 95%CI: 1.38-2.55, P < 0.001; HR = 2.19, 95%CI: 1.64-2.94, P < 0.001) and DFS (HR = 1.67, 95%CI: 1.37-2.04, P < 0.001; HR = 2.50, 95%CI: 1.39-4.48, P < 0.001). However, no significant relationship of PLR and LMR and OS (P = 0.085; P = 0.338) and DFS (P = 0.396; P = 0.124) was observed. CONCLUSION: Higher NLR and GPS were related with worse prognosis and might serve as novel prognostic indicators for osteosarcoma patients.