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The Effect of Rheumatoid Arthritis on Features Associated with Sarcopenia: A Mendelian Randomization Study

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Abstract

Previous epidemiological evidence suggests rheumatoid arthritis is associated with sarcopenia-related features. However, most of the current evidence is from cross-sectional studies, and the causal link of this association is still to be determined. Therefore, this study was committed to a two-sample Mendelian randomization analysis to assess the causal effect of rheumatoid arthritis on sarcopenia-related features. In this two-sample Mendelian randomization study, instrumental variables for rheumatoid arthritis were obtained from the Non-Cancer Disease Study, and data for the five relevant characteristics of sarcopenia were pooled from UKBiobank. Inverse variance weighting is the primary analysis method for assessing causal effects. MR-Egger regression and weighted median are complementary analysis methods for causal effects. Leave-one-out analysis, horizontal pleiotropy test, and Heterogeneity test are applied as a sensitivity analysis to assess the robustness of causal effect estimates. The inverse variance weighted results for the five characteristics associated with sarcopenia and rheumatoid arthritis were: hand grip strength (right) (beta = − 2.309, se = 0.206, p = 3.340E-29), hand grip strength (left) (beta = − 2.046, se = 0.205, p = 2.166E-23), whole body lean mass (beta = − 0.843, se = 0.135, p = 4.67E-10), appendicular lean mass (beta = − 2.444, se = 0.208, p = 6.069E-32), Usual walking pace (OR 0.340, 95% CI (0.238, 0.484), p = 2.471E-09). The sensitivity analyses did not support that horizontal pleiotropy distorted causal effect estimates. The beta coefficient quantifies the number of standard deviations of the continuous outcome variables (hand grip strength, whole body lean mass, and appendicular lean mass) that change on average with each increase in the standard deviation of the binary exposure variable (rheumatoid arthritis). The odds ratios indicate the increased risk of the binary outcome variable (usual walking pace) per rheumatoid arthritis standard deviation increase. This study has demonstrated a negative causal effect of rheumatoid arthritis with five major sarcopenia-related features in a European population.

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We have provided a catalog and zip file of supplementary files. For all supplemental pictures, tables, and a supplemental file catalog, readers can obtain them from this zip.

Abbreviations

EWGSOP2:

European Working Group on Sarcopenia in Older People 2 

GWAS:

Genome-wide association studies

IVs:

Instrumental variables

IVW:

Inverse variance-weighted

MR:

Mendelian randomization

MR-PRESSO:

Mendelian randomization pleiotropy residual sum and outlier

RA:

Rheumatoid arthritis

SNPs:

Single nucleotide polymorphisms

TNF-α:

Tumor necrosis factor-alpha

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Acknowledgements

We thank Professor Jing Zhang from the Department of Geriatrics, Chengdu University of Traditional Chinese Medicine Hospital, for her detailed review of the initial version of this manuscript and the feedback she gave.

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Authors and Affiliations

  1. School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China

    Kaixi Ding, Wei Jiang & Juejue Zhangwang

  2. Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China

    Wei Jiang, Juejue Zhangwang & Ming Lei

  3. Department of Neurosurgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China

    Jian Li

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Contributions

“Conceptualization, Kaixi Ding. And Wei Jiang.; methodology, Kaixi Ding. And Wei Jiang.; software, Juejue Zhangwang. And Jian Li.; validation, Juejue Zhangwang., Kai Ding.; writing—original draft preparation, Kaixi Ding.; writing—review and editing, Kaixi Ding. And Wei Jiang.; visualization, Wei Jiang.; supervision, Ming Lei.; project administration, Ming Lei. And Jian Li.

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Correspondence to Ming Lei.

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Kaixi Ding, Wei Jiang, Juejue Zhangwang, Jian Li, and Ming Lei have declare no competing interests.

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Ding, K., Jiang, W., Zhangwang, J. et al. The Effect of Rheumatoid Arthritis on Features Associated with Sarcopenia: A Mendelian Randomization Study. Calcif Tissue Int 114, 286–294 (2024). https://doi.org/10.1007/s00223-023-01178-w

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