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A bi-directional Mendelian randomization study of the sarcopenia-related traits and osteoporosis.

ABSTRACT: Both sarcopenia and osteoporosis are common geriatric diseases causing huge socioeconomic burdens, and clinically, they often occur simultaneously. Observational studies have found a controversial correlation between sarcopenia and osteoporosis and their causal relationship is not clear. Therefore, we performed a bi-directional two-sample Mendelian randomization (MR) analysis to assess the potential causal relationship between sarcopenia-related traits (hand grip strength, lean mass, walking pace) and osteoporosis. Our analysis was performed by applying genetic variants obtained from the UK Biobank and the GEnetic Factors for OSteoporosis (GEFOS) datasets. We used inverse-variance weighted (IVW) and several sensitivity analyses to estimate and cross-validate the potential causal relationship in this study. We found that bone mineral density (BMD) was causally positively associated with left-hand grip strength (β = 0.017, p-value = 0.001), fat-free mass (FFM; right leg FFM, β = 0.014, p-value = 0.003; left arm FFM, β = 0.014, p-value = 0.005), but not walking pace. Higher hand grip strength was potentially causally associated with increased LS-BMD (right-hand grip strength, β = 0.318, p-value = 0.001; left-hand grip strength, β = 0.358, p-value = 3.97 × 10-4). In conclusion, osteoporosis may be a risk factor for sarcopenia-related traits and muscle strength may have a site-specific effect on BMD.

SUBMITTER: Ma XY

PROVIDER: S-EPMC9365559 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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A bi-directional Mendelian randomization study of the sarcopenia-related traits and osteoporosis.

Ma Xue-Ying XY Liu Hui-Min HM Lv Wan-Qiang WQ Qiu Chuan C Xiao Hong-Mei HM Deng Hong-Wen HW

Aging 20220702 14

Both sarcopenia and osteoporosis are common geriatric diseases causing huge socioeconomic burdens, and clinically, they often occur simultaneously. Observational studies have found a controversial correlation between sarcopenia and osteoporosis and their causal relationship is not clear. Therefore, we performed a bi-directional two-sample Mendelian randomization (MR) analysis to assess the potential causal relationship between sarcopenia-related traits (hand grip strength, lean mass, walking pac ...[more]

PMID: 35780076

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Project description:BackgroundObservational studies have suggested associations between serum urate levels and sarcopenia, but the causality underlying this correlation remains uncertain. The principal objective of this study is to investigate a causal relationship of serum urate levels with sarcopenia-related traits (hand grip strength, lean mass, walking pace) using bidirectional two-sample Mendelian randomization (MR) approach. The utilization of MR methodology serves to minimize bias caused by reverse causality and confounding factors from observational studies.MethodsThe summary statistics of serum urate levels were derived from a cohort consisting of 288,659 individuals participating in CKDGen study. The parameters of right-hand grip strength (N=461,089), left-hand grip strength (N=461,026), appendicular lean mass (ALM) (N=450,243), whole-body lean mass(N=454,850),right-leg fat-free mass(FFM;N=454,835),left-leg FFM(N=454,805), right-arm FFM(N=454,753),left-arm FFM(N=454,672) and walking pace (N=459,915)were sourced from the UK Biobank. MR analysis was conducted utilizing inverse variance weighted (IVW), weighted median, and MR-Egger to evaluate causality. Sensitivity analysis was performed using Cochran's Q test, MR-Egger intercept test, leave-one-out analysis and the funnel plot.ResultsIVW estimates demonstrated that serum urate levels exhibited no causal association with sarcopenia-related traits. In the inverse MR investigation, we had exclusively discerned an inverse correlation between walking pace and serum urate levels. No compelling evidence had surfaced to substantiate any association of other sarcopenia-related traits with serum urate. Supplemental MR methods consistently validated the findings obtained from the primary analysis. Sensitivity analysis demonstrated the robustness of findings.ConclusionOur MR study revealed the absence of the bidirectional causal relationship between serum urate levels and sarcopenia. It is imperative to acknowledge that advanced age and an individual's health status are pivotal determinants influencing urate level and the initiation and advancement of sarcopenia. However, it is worth underscoring that these aspects remain unexamined within the purview of this study. Thus, future investigations should delve deeper into these intricate facets.

Project description:BackgroundThe two geriatric diseases, sarcopenia and cardiovascular disease (CVD), often coexist, yet the causal relationship is unclear. However, few studies focus on the effect of muscle mass on CVD. This comprehensive study is dedicated to unearthing the potential connection between sarcopenia-related traits and CVD at the genetic level.MethodA two-sample bi-directional Mendelian randomization (MR) study was conducted. In the first stage, we performed MR analysis regarding coronary heart disease (CHD), stroke, and myocardial infarction (MI) as exposure factors to reveal their effect on appendicular lean mass (ALM) and hand grip strength. In the second stage, we reverse the position of exposures and outcomes. The inverse variance weighted (IVW) method was used as the primary approach to reveal the potential causation between the exposure and outcome.ResultsThe results of the IVW method revealed a negative causal effect of ALM on CHD (OR = 0.848, 95% CI = 0.804 to 0.894, p = 8.200E-10), stroke (OR = 0.931, 95% CI = 0.890 to 0.975, p = 2.220E-03), and MI (OR = 0.810, 95% CI = 0.694 to 0.901, p = 1.266E-13). Additionally, the left-hand grip strength is a significant protective factor for CHD (OR = 0.737, 95% CI = 0.601 to 0.904, p = 3.353E-03) and MI (OR = 0.631, 95% CI = 0.515 to 0.765, p = 2.575E-06), but is not causally linked to the stroke (OR = 0.971, 95% CI =0.829 to 1.139, p = 0.720). Meanwhile, the same conclusion about the effect of right-hand grip strength on CHD (OR = 0.681, 95% CI = 0.558 to 0.832, p = 1.702E-05), MI (OR = 0.634, 95% CI = 0.518 to 0.776, p = 9.069E-06), and stroke (OR = 1.041, 95% CI = 0.896 to 1.209, p = 0.604) was obtained. However, no significant causal effect of CVD (CHD, stroke, MI) on sarcopenia-related traits (ALM, handgrip strength) was found.ConclusionThere is a unidirectional causal relationship between sarcopenia and CVD. The loss of muscle mass and strength has a significant causal role in promoting the occurrence and development of CVD, providing a reference for the prevention and treatment of comorbidities in older people.

Dataset Information

A bi-directional Mendelian randomization study of the sarcopenia-related traits and osteoporosis.

Publications

A bi-directional Mendelian randomization study of the sarcopenia-related traits and osteoporosis.

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