An insight into the causal relationship between sarcopenia-related traits and venous thromboembolism: A mendelian randomization study

Xinchao Du; Zhiwei Yao; Dongwei Wang; Xinwei Dong; Juncai Bai; Yingchun Gu; Yaohua Yu; Weifeng Zhang; Qingxia Qi; Shengyuan Gu

doi:10.1371/journal.pone.0303148

An insight into the causal relationship between sarcopenia-related traits and venous thromboembolism: A mendelian randomization study

PLoS One. 2024 May 16;19(5):e0303148. doi: 10.1371/journal.pone.0303148. eCollection 2024.

Authors

Xinchao Du¹, Zhiwei Yao², Dongwei Wang³, Xinwei Dong¹, Juncai Bai³, Yingchun Gu³, Yaohua Yu⁴, Weifeng Zhang⁵, Qingxia Qi¹, Shengyuan Gu¹

Affiliations

¹ Department of Cardiology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China.
² Department of Thyroid Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, China.
³ Department of Cardiac Rehabilitation, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China.
⁴ Department of Respiratory Medicine and Pulmonary Rehabilitation, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China.
⁵ Department of Rheumatism and Immunology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China.

Abstract

Background: As a geriatric syndrome, sarcopenia has a high prevalence in the old population and represents an impaired state of health with adverse health outcomes. A strong clinical interest in its relationship with venous thromboembolism (VTE), which is a complex trait disease with a heterogeneous annual incidence rate in different countries, has emerged. The relationship between sarcopenia and venous thromboembolism has been reported in observational studies but the causality from sarcopenia to VTE remained unclarified. We aimed to assess the causal effect of sarcopenia on the risk of VTE with the two-sample Mendelian randomization (MR) method.

Methods: Two sets of single-nucleotide polymorphisms (SNPs), derived from two published genome-wide association study (GWAS) meta-analyses and genetically indexing muscle weakness and lean muscle mass separately, were pooled into inverse variance weighted (IVW), weighted median and MR-Egger analyses.

Results: No evidence was found for the causal effect of genetically predicted muscle weakness (IVW: OR = 0.90, 95% CI = 0.76-1.06, p = 0.217), whole body lean mass (IVW: OR = 1.01, 95% CI = 0.87-1.17, p = 0.881) and appendicular lean mass (IVW: OR = 1.13, 95% CI = 0.82-1.57, p = 0.445) on the risk of VTE. However, both genetically predicted whole-body lean mass and appendicular lean mass can causally influence diabetes mellitus (IVW of whole-body lean mass: OR = 0.87, 95% CI = 0.78-0.96, p = 0.008; IVW of appendicular lean mass: OR = 0.71, 95% CI = 0.54-0.94, p = 0.014) and hypertension (IVW of whole-body lean mass: OR = 0.92, 95% CI = 0.87-0.98, p = 0.007; IVW of appendicular lean mass: OR = 0.84, 95% CI = 0.73-0.96, p = 0.013).

Conclusions: Genetically predicted sarcopenia does not causally influence VTE directly, but it might still have an indirect effect on VTE incidence via diabetes mellitus and hypertension.

Copyright: © 2024 Du et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Genome-Wide Association Study*
Humans
Mendelian Randomization Analysis*
Polymorphism, Single Nucleotide*
Risk Factors
Sarcopenia* / complications
Sarcopenia* / epidemiology
Sarcopenia* / genetics
Venous Thromboembolism* / epidemiology
Venous Thromboembolism* / etiology
Venous Thromboembolism* / genetics

Grants and funding

Z.Y. SDYWZGKCJHLH2023096 to Zhiwei Yao. The joint initiation project of scientific and technological innovation for Shandong Province medical staff. There is no URL for the above funder. No, this study was independent of any sponsors or funders.