Causal associations between thyroid function and sarcopenia-related traits: a Mendelian randomization study

As the global population ages, the incidence of sarcopenia increases, resulting in increasing numbers of patients with impairments in physical function. Thyroid function disorders may contribute to the pathogenesis of sarcopenia. This study aimed to establish a causal relationship between thyroid hormones (TH) and sarcopenia using a two-sample Mendelian randomization (MR) analysis method.

A two-sample MR study was conducted using summary-level data from genome-wide association studies (GWAS) which included publicly available pooled statistics for thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and the FT3 to FT4 ratio from the Thyroidomics Consortium, as well as summary statistics for sarcopenia-related traits, such as appendicular lean mass (ALM), whole-body lean mass (WBLM), grip strength (left and right), and walking pace from the UK Biobank. The MR analysis used genetic exposure tools for assessment of thyroid function (TSH, FT4, FT3, and the FT3 to FT4 ratio) and outcome measures for sarcopenia (ALM, WBLM, grip strength, and walking pace). The inverse variance weighted method was employed to estimate the genetic predictions of the causal effect of thyroid function on sarcopenia risk. Sensitivity analyses were also conducted to validate the reliability of the MR results.

Correlations were observed between ALM and several indicators, as follows: TSH (OR: 1.03; 95% CI: 1.01-1.04), FT4 (OR: 0.95; 95% CI: 0.93-0.98), FT3 (OR: 1.09; 95% CI: 1.03-1.15), and the FT3 to FT4 ratio (OR: 1.25; 95% CI: 1.11-1.42). Furthermore, causal relationships were identified between WBLM and TSH (OR: 1.02; 95% CI: 1.01-1.03), as well as low TSH (OR: 0.99; 95% CI: 0.99-1.00) and high TSH (OR: 0.97; 95% CI: 0.96-1.00). Walking pace was associated with low TSH (OR: 0.99; 95% CI: 0.99-1.00), whereas grip strength was related to TSH (OR: 1.01; 95% CI: 1.00-1.02) and low TSH (OR: 0.99; 95% CI: 0.99-1.00). High TSH (OR: 1.04; 95% CI: 1.01-1.08) and FT3 (OR: 0.96; 95% CI: 0.92-1.00) levels were associated with right grip strength.

These results indicate a causal relationship between thyroid function and sarcopenia, highlighting FT3 and the FT3 to FT4 ratio as key indicators. However, total triiodothyronine (TT3) emerges as a potential indicator that requires further investigation in future studies.