Dataset Information

[Increased muscle mass increases risks of intervertebral disc degeneration: a two-sample Mendelian randomization study].

ABSTRACT:

Objective

To investigate the causal relationship between sarcopenia (SP) and intervertebral disc degeneration (IVDD) using two-sample Mendelian randomization analysis.

Methods

Genome-wide association study (GWAS) databases of SP (lean body mass, right and left hand grip strength) and IVDD were obtained. The single nucleotide polymorphisms (SNPs) strongly associated with exposure were obtained as an instrumental variable. After conservatively removing two confounders (smoking and sedentary life style), the causal relationship between SP and IVDD was assessed using Mendelian randomization analyses through the inverse variance weighting (IVW), weighted median (WM) and MR-Egger methods. The consistency and accuracy of the results were verified by MR-PRESSO, double validation, negative control, heterogeneity and diversity tests.

Results

A total of 570 SNPs associated with lean muscle mass, 97 with strong right hand grip strength, and 79 with strong left hand grip strength were included in the analysis. The results showed that lean muscle mass had a significant positive correlation with IVDD (IVW: OR=1.139, 95% CI: 1.076-1.204, P=6.619e-6) and right hand grip strength had a possible positive correlation with IVDD. After reanalysis in MR-PRESSO and selection of a new IVDD database, the results remained largely consistent with the previous results.

Conclusion

Increased muscle mass may increase the risk of intervertebral disc degeneration.

SUBMITTER: Su C

PROVIDER: S-EPMC10774104 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

[Increased muscle mass increases risks of intervertebral disc degeneration: a two-sample Mendelian randomization study].

Su C C Tian Y Y Zhang Q Q Wan T T Xia D D

Nan fang yi ke da xue xue bao = Journal of Southern Medical University 20231201 12

<h4>Objective</h4>To investigate the causal relationship between sarcopenia (SP) and intervertebral disc degeneration (IVDD) using two-sample Mendelian randomization analysis.<h4>Methods</h4>Genome-wide association study (GWAS) databases of SP (lean body mass, right and left hand grip strength) and IVDD were obtained. The single nucleotide polymorphisms (SNPs) strongly associated with exposure were obtained as an instrumental variable. After conservatively removing two confounders (smoking and s ...[more]

PMID: 38189388

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Project description:BackgroundAlthough previous studies have suggested a close association between gut microbiota (GM) and intervertebral disc degeneration (IVDD), the causal relationship between them remains unclear. Hence, we thoroughly investigate their causal relationship by means of a two-sample Mendelian randomization (MR) study, aiming to determine the impact of gut microbiota on the risk of developing intervertebral disc degeneration.MethodsSummary data from genome-wide association studies of GM (the MiBioGen) and IVDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. A reverse MR analysis was conducted to assess potential reverse causation.ResultsWe identified nine gut microbial taxa that were causally associated with IVDD (P < 0.05). Following the Benjamini-Hochberg corrected test, the association between the phylum Bacteroidetes and a higher risk of IVDD remained significant (IVW FDR-corrected P = 0.0365). The results of the Cochrane Q test did not indicate heterogeneity (P > 0.05). Additionally, both the MR-Egger intercept test and the MR-PRESSO global test revealed that our results were not influenced by horizontal pleiotropy (P > 0.05). Furthermore, the leave-one-out analysis substantiated the reliability of the causal relationship. In the reverse analysis, no evidence was found to suggest that IVDD has an impact on the gut microbiota.ConclusionOur results validate the potential causal impact of particular GM taxa on IVDD, thus providing fresh insights into the gut microbiota-mediated mechanism of IVDD and laying the groundwork for further research into targeted preventive measures.

Project description:BackgroundAlthough previous studies have suggested a possible association between bone mineral density (BMD) and intervertebral disc degeneration (IDD), the causal relationship between them remains unclear. Evidence from accumulating studies indicates that they might mutually influence one another. However, observational studies may be affected by potential confounders. Meanwhile, Mendelian randomization (MR) study can overcome these confounders to assess causality.ObjectivesThis Mendelian randomization (MR) study aimed to explore the causal effect of bone mineral density (BMD) on intervertebral disc degeneration (IDD).MethodsSummary data from genome-wide association studies of bone mineral density (BMD) and IDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. Multivariate MR (MVMR) analyses used multivariable inverse variance-weighted methods to individually and jointly adjust for four potential confounders, body mass index (BMI), Type2 diabetes, hyperthyroidism and smoking. A reverse MR analysis was conducted to assess potential reverse causation.ResultsIn the univariate MR analysis, femoral neck bone mineral density (FNBMD), heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) had a direct causal effect on intervertebral disc degeneration (IDD) [FNBMD-related analysis: OR(95%CI) = 1.17 (1.04 to 1.31), p = 0.008, eBMD-related analysis: OR(95%CI) = 1.06 (1.01 to 1.12), p = 0.028, LSBMD-related analysis: OR(95%CI) = 1.20 (1.10 to 1.31), p = 3.38E-7,TB BMD-related analysis: OR(95%CI) = 1.20 (1.12 to 1.29), p = 1.0E-8]. In the MVMR analysis, it was revealed that, even after controlling for confounding factors, heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) still maintained an independent and significant causal association with IDD(Adjusting for heel bone mineral density: beta = 0.073, OR95% CI = 1.08(1.02 to 1.14), P = 0.013; Adjusting for lumbar spine bone mineral density: beta = 0.11, OR(95%CI) = 1.12(1.02 to 1.23), P = 0.03; Adjusting for total body bone mineral density: beta = 0.139, OR95% CI = 1.15(1.06 to 1.24), P = 5.53E - 5). In the reverse analysis, no evidence was found to suggest that IDD has an impact on BMD.ConclusionsThe findings from our univariate and multivariable Mendelian randomization analysis establish a substantial positive causal association between BMD and IDD, indicating that higher bone mineral density may be a significant risk factor for intervertebral disc degeneration. Notably, no causal effect of IDD on these four measures of bone mineral density was observed. Further research is required to elucidate the underlying mechanisms governing this causal relationship.

Dataset Information

[Increased muscle mass increases risks of intervertebral disc degeneration: a two-sample Mendelian randomization study].

Objective

Methods

Results

Conclusion

Publications

[Increased muscle mass increases risks of intervertebral disc degeneration: a two-sample Mendelian randomization study].

Similar Datasets

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