Thyroid function, physical activity and sedentary behaviour: A bidirectional two-sample Mendelian randomisation study.

Background: The interinfluence of thyroid function and daily physical activity (PA) remains unclear. We examined the causal relationship between genetically proxied thyroid-related traits; hypothyroidism, hyperthyroidism, thyroid stimulating hormone (TSH) and free thyroxine (FT4), and daily PA measures; leisure screen time (LST) and moderate-to-vigorous physical activity (MVPA), using Mendelian randomisation (MR) analysis.

Methods: We used genome-wide association study (GWAS) data from the ThyroidOmics Consortium and the most comprehensive meta-analysis on PA, comprising data on hypothyroidism (n = 53 423), hyperthyroidism (n = 51 823), TSH within the reference range (n = 54 288), fT4 within the reference range (n = 49 269), LST (n = 526 725), and MVPA (n = 608 595) to conduct a bidirectional two-sample MR analysis. The inverse variance weighted (IVW) method was employed as the primary result. Sensitivity analyses included MR-Egger, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO) regression. Similar investigations were conducted in the reverse direction. Finally, we analysed a multivariable MR using body mass index (BMI)-related traits GWAS data.

Results: In the primary IVW analysis, an increase in genetically proxied TSH levels significantly increased LST (correlation coefficient (β) = 0.040; 95% confidence interval (CI) = 0.020-0.061, P = 9.776 × 10^-5). The multivariable MR analysis indicated that the positive causal effect still existed when considering the influence of BMI (MVMR-IVW: β = 0.042; 95% CI = 0.011-0.073, P = 0.007). Conversely, there was no evidence to suggest that PA impacts thyroid function.

Conclusions: The results of this MR analysis suggest that thyroid function influences daily PA. The positive association between TSH and LST is not confounded or mediated by BMI.