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Causal relationship between sarcopenia with osteoarthritis and the mediating role of obesity: a univariate, multivariate, two-step Mendelian randomization study.
Jin, Zicheng; Wang, Rui; Jin, Linzi; Wan, Lishuang; Li, Yuzhou.
Afiliação
  • Jin Z; College of Physical Education, Henan Normal University, Xinxiang, 453007, China.
  • Wang R; College of Physical Education, Henan Normal University, Xinxiang, 453007, China.
  • Jin L; College of Music and Dance, Henan Normal University, Xinxiang, 453007, China.
  • Wan L; College of Physical Education, Henan Normal University, Xinxiang, 453007, China.
  • Li Y; College of Physical Education, Henan Normal University, Xinxiang, 453007, China. yuzhouli2003@163.com.
BMC Geriatr ; 24(1): 469, 2024 May 29.
Article em En | MEDLINE | ID: mdl-38811889
ABSTRACT

BACKGROUND:

Recent genetic evidence supports a causal role for sarcopenia in osteoarthritis, which may be mediated by the occurrence of obesity or changes in circulating inflammatory protein levels. Here, we leveraged publicly available genome-wide association study data to investigate the intrinsic causal relationship between sarcopenia, obesity, circulating inflammatory protein levels, and osteoarthritis.

METHODS:

In this study, we used Mendelian randomization analyses to explore the causal relationship between sarcopenia phenotypes (Appendicular lean mass [ALM], Low hand-grip strength [LHG], and usual walking pace [UWP]) and osteoarthritis (Knee osteoarthritis [KOA], and Hip osteoarthritis [HOA]). Univariable Mendelian randomization (UVMR) analyses were performed using the inverse variance weighted (IVW) method, MR-Egger, weighted median method, simple mode, and weighted mode, with the IVW method being the primary analytical technique. Subsequently, the independent causal effects of sarcopenia phenotype on osteoarthritis were investigated using multivariate Mendelian randomization (MVMR) analysis. To further explore the mechanisms involved, obesity and circulating inflammatory proteins were introduced as the mediator variables, and a two-step Mendelian randomization analysis was used to explore the mediating effects of obesity and circulating inflammatory proteins between ALM and KOA as well as the mediating proportions.

RESULTS:

UVMR analysis showed a causal relationship between ALM, LHG, UWP and KOA [(OR = 1.151, 95% CI 1.087-1.218, P = 1.19 × 10-6, PFDR = 7.14 × 10-6) (OR = 1.215, 95% CI 1.004-1.470; P = 0.046, PFDR = 0.055) (OR = 0.503, 95% CI 0.292-0.867; P = 0.013, PFDR = 0.027)], and a causal relationship between ALM, UWP and HOA [(OR = 1.181, 95% CI 1.103-1.265, P = 2.05 × 10-6, PFDR = 6.15 × 10-6) (OR = 0.438, 95% CI 0.226-0.849, P = 0.014, PFDR = 0.022)]. In the MVMR analyses adjusting for confounders (body mass index, insomnia, sedentary behavior, and bone density), causal relationships were observed between ALM, LHG, UWP and KOA [(ALM OR = 1.323, 95%CI 1.224- 1.431, P = 2.07 × 10-12), (LHG OR = 1.161, 95%CI 1.044- 1.292, P = 0.006), (UWP OR = 0.511, 95%CI 0.290- 0.899, P = 0.020)], and between ALM and HOA (ALM OR = 1.245, 95%CI 1.149- 1.348, P = 7.65 × 10-8). In a two-step MR analysis, obesity was identified to play a potential mediating role in ALM and KOA (proportion mediated 5.9%).

CONCLUSIONS:

The results of this study suggest that decreased appendicular lean mass, grip strength, and walking speed increase the risk of KOA and decreased appendicular lean mass increases the risk of HOA in patients with sarcopenia in a European population. Obesity plays a mediator role in the occurrence of KOA due to appendicular lean body mass reduction.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Estudo de Associação Genômica Ampla / Sarcopenia / Análise da Randomização Mendeliana / Obesidade Limite: Aged / Female / Humans / Male Idioma: En Revista: BMC Geriatr Assunto da revista: GERIATRIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Estudo de Associação Genômica Ampla / Sarcopenia / Análise da Randomização Mendeliana / Obesidade Limite: Aged / Female / Humans / Male Idioma: En Revista: BMC Geriatr Assunto da revista: GERIATRIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China