Systemic lupus erythematosus Association between Osteomyelitis: A two-sample Mendelian randomization study in European population

Hu, Minhua; Sun, Zhizhong; Tang, Xintao; Zeng, Wenxing; Yan, Hongsong; Jiang, Ziwei; Huang, Feng

doi:10.1016/j.heliyon.2023.e22999

Cited by 2 publications

References 33 publications

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Causal effects of the RANK-RANKL-OPG system and scoliosis: A bidirectional 2-sample Mendelian randomization study

Xie,

Wan,

Liu

et al. 2024

Medicine

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Epidemiological studies and a recent Mendelian randomization (MR) study have identified an association between low bone mass and an increased risk of scoliosis. Previous research suggests that bone loss in patients with scoliosis may be related to the RANK-RANKL-OPG system. This study is to investigate whether a causal relationship exists between the RANK-RANKL-OPG system and the development of scoliosis. Genome-wide association study (GWAS) data for RANK and RANKL were sourced from the UK Biobank’s Pharmaceutical Proteomics Project, while OPG data were derived from 2 independent cohorts, and scoliosis data from the FinnGen R10 database. A bidirectional 2-sample MR framework was applied to investigate causal relationships between OPG, RANK, RANKL, and scoliosis, with inverse variance weighting (IVW) as the main analytical method. Meta-analysis was used to integrate findings across cohorts, and multiple sensitivity analyses were conducted to assess the robustness and reliability of the results. According to the IVW results, there was no significant causal relationship between RANK (OR = 0.973, 95% CI = 0.871–1.087, P = .626) and RANKL (OR = 1.048, 95% CI = 0.938–1.171, P = .411) and scoliosis. OPG is a potential protective factor for scoliosis (Folkersen 2020 OR = 0.739, 95% CI = 0.611–0.893, P = .002; Zhao 2023 OR = 0.833, 95% CI = 0.716–0.968, P = .017).The results of Meta-analysis also showed OPG (P = 1.428e−4) would reduce the risk of scoliosis. Inverse MR analysis showed no statistically significant causal relationship between scoliosis and RANK, RANKL and OPG levels (P > .05). Our study employing MR methodology provides robust evidence supporting a causal relationship between decreased osteoprotegerin (OPG) levels and increased susceptibility to scoliosis. However, no significant relationship was found between scoliosis with the RANK-RANKL-OPG system. This research establishes a basis for further exploration of the pathophysiological mechanisms and potential targeted treatments for scoliosis. Future studies are necessary to understand how OPG influences the development of scoliosis.

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Causal effects of the RANK-RANKL-OPG system and scoliosis: A bidirectional 2-sample Mendelian randomization study

Xie,

Wan,

Liu

et al. 2024

Medicine

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Causal association of immune cell phenotypes with osteosarcoma and the mediation role of blood metabolites: A two-steps, two-samples Mendelian randomization study

Niu,

Xu,

Wang

et al. 2024

Preprint

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Background: Immunogenic nature of osteosarcoma is well-established, but the precise roles of immune cells and the potential influence of blood metabolites on its advancement remain unclear. Methods: Two-step, two-sample Mendelian randomization (MR) strategy was employed to investigate causal relation between osteosarcoma risk and immune cell distribution, we sought to uncover and measure the potential mediating role of blood metabolites. Our analysis incorporated a diverse range of MR estimation techniques, encompassing inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted mode, and simple mode. Additionally, we conducted sensitivity analyses to assess the reliability of our results. Results: MR analysis revealed that three immune cell phenotypes exhibited positive relation with osteosarcoma risk (CX3CR1 on CD14- CD16-, CD25 on CD45RA- CD4 not Treg, and CD45 on HLA DR+ CD8br), while four immune cell phenotypes illustrated negative relation to osteosarcoma risk (BAFF-R on IgD+ CD38- unsw mem, CD20 on IgD- CD38-, Naive CD4+ %T cell, and CD28+ CD45RA+ CD8br %CD8br). Moreover, mediation MR analysis demonstrated causal effect of CX3CR1 on CD14- CD16- within monocyte panel on osteosarcoma (Total effect IVW: OR = 0.3330) was predominantly mediated by dimethyl sulfone (0.0288, constituting 8.70% of Total effect) and unidentified metabolite X-12680 (0.0524, constituting 15.74% of Total effect). Conclusions: This investigation unveiled a causal link between immune cells and osteosarcoma, potentially mediated by blood metabolites.

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Systemic lupus erythematosus Association between Osteomyelitis: A two-sample Mendelian randomization study in European population

Cited by 2 publications

References 33 publications

Causal effects of the RANK-RANKL-OPG system and scoliosis: A bidirectional 2-sample Mendelian randomization study

Causal effects of the RANK-RANKL-OPG system and scoliosis: A bidirectional 2-sample Mendelian randomization study

Causal association of immune cell phenotypes with osteosarcoma and the mediation role of blood metabolites: A two-steps, two-samples Mendelian randomization study

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