Genetic insights into dietary patterns, liposome mediation, and osteoporosis risk: a Mendelian randomization study.

Background: This study examines the indirect causal relationships between dietary habits and osteoporosis, mediated through liposomes, utilizing a two-sample Mendelian randomization (MR) approach. The research leverages genetic variations as instrumental variables to explore the genetic influences on dietary habits, liposomes, and osteoporosis, aiming to unravel the complex interplay between diet, lipid metabolism, and bone health. Methods: The study utilized genome-wide association studies (GWAS) data for liposomes from Finnish individuals and osteoporosis-related data, alongside dietary factors from the OpenGWAS database. Instrumental variables were selected based on genetic variants associated with these factors, using a strict significance level and linkage disequilibrium threshold. Statistical analysis employed the Inverse Variance Weighted method, weighted median, and mode-based methods within the R environment, complemented by sensitivity analyses to ensure the robustness of the causal inferences. Results: Findings revealed significant causal relationships between specific dietary components (white rice, cereal, and non-oily fish) and osteoporosis risk, both directly and mediated through changes in liposome levels. Notably, white rice consumption was associated with an increased risk of osteoporosis, while cereal and non-oily fish intake showed protective effects. Further, certain liposomes were identified as mediators in these relationships, suggesting a link between diet, lipid profiles, and bone health. Conclusion: The study highlights the significant impact of dietary habits on osteoporosis risk, mediated through liposomes. These findings underscore the importance of considering lipidomic profiles in dietary guidance and suggest potential targets for preventing osteoporosis through nutritional interventions.

The relationship between metabolite mediated immune regulatory imbalance and the occurrence of malignant tumors of bone and articular cartilage: a Mendelian randomization study.

Background: This study aims to assess the causal relationship between immune cell characteristics and malignant tumors of bone and articular cartilage, focusing on the mediating role of metabolites. Using Mendelian randomization, we evaluated these relationships based on genetic variations to identify potential biomarkers and therapeutic targets. Methods: A two-sample Mendelian randomization analysis was conducted using GWAS data for immune cell features and 1,400 metabolites to investigate direct and mediating effects. Effective instrumental variables (IVs) were selected, and statistical analyses-including inverse variance weighting (IVW), weighted median, and mode-based methods-were performed using R software. This approach enabled the assessment of direct causal relationships as well as the potential mediating role of metabolites in the association between immune cell features and malignancies. Results: Significant causal relationships were identified between 26 immune phenotypes and the risk of malignant tumors of bone and articular cartilage. Notably, the HLA DR+ NK cell phenotype SSC-A showed a positive correlation with the risk of these malignancies. Further analysis revealed causal relationships with 67 metabolites, 38 of which were positively correlated and 29 negatively correlated. Mediation analysis highlighted the role of immune surveillance and metabolic dysregulation in tumor development, as evidenced by the association between the immune phenotype SSC-A on HLA DR+ NK cells and the metabolite 5-hydroxyhexanoate. Conclusion: The findings suggest significant causal relationships between immune phenotypes and malignant tumors of bone and articular cartilage, with metabolites potentially mediating these relationships. These insights lay the groundwork for further research and could contribute to the development of new biomarkers and treatment strategies.

Exploring the immunological landscape of osteomyelitis through mendelian randomization analysis.

Background: Osteomyelitis is a severe bone marrow infection, whose pathogenesis is not yet fully understood. This study aims to explore the causal relationship between immune cell characteristics and osteomyelitis, hoping to provide new insights for the prevention and treatment of osteomyelitis. Methods: Based on two independent samples, this study employed a two-sample Mendelian randomization (MR) analysis to assess the causal relationship between 731 immune cell characteristics (divided into seven groups) and osteomyelitis. Genetic variants were used as proxies for risk factors to ensure that the selected instrumental variables meet the three key assumptions of MR analysis. Genome-Wide Association Studies (GWAS) data for immune characteristics were obtained from the public GWAS catalog, while data for osteomyelitis was sourced from the FinnGen. Results: At a significance level of 0.05, 21 immune phenotypes were identified as having a causal relationship with osteomyelitis development. In the B cell group, phenotypes such as Memory B cell % B cell (percentage of memory B cells within the total B cell population, % finger cell ratio), CD20- %B cell (percentage of B cells that do not express the CD20 marker on their surface), and Memory B cell % lymphocyte showed a positive causal relationship with osteomyelitis, while Naive-mature B cell %B cell and IgD-CD38-absolute cell counts (AC) phenotypes showed a negative causal relationship. In addition, specific immune phenotypes in the conventional dendritic cells (cDCs) group, Myeloid cell group, TBNK (T cells, B cells, natural killer cells) cell group, T cell maturation stage, and Treg cell group also showed significant associations with osteomyelitis. Through reverse MR analysis, it was found that osteomyelitis had no significant causal impact on these immune phenotypes, suggesting that the occurrence of osteomyelitis may not affect these immune cell phenotypes. Conclusion: To our knowledge, this is the first study to shed light on the causal relationship between specific immune cell characteristics and the development of osteomyelitis, thereby providing a new perspective to understand the immune mechanism of osteomyelitis. These findings are significant for formulating targeted prevention and treatment strategies, and hold promise to improve the treatment outcomes for patients with osteomyelitis.