Causal Association between Serum Thyroid-Stimulating Hormone and Obesity: A Bidirectional Mendelian Randomization Study

Context The association between serum thyroid-stimulating hormone (TSH) and obesity traits has been investigated previously in several epidemiological studies. However, the underlying causal association has not been established. Objective To determine and analyze the causal association between serum TSH level and obesity-related traits (BMI and obesity). Design, setting, participants The latest genome-wide association studies (GWASs) on TSH, BMI and obesity were searched to obtain full statistics. Bidirectional two-sample Mendelian randomization (MR) was performed to explore the causal relationship between serum TSH and BMI and obesity. The inverse variance-weighted (IVW) and MR-Egger methods were used to combine the estimation for each SNP. Based on the preliminary MR results, free thyroxine (fT4) and free triiodothyronine (fT3) levels were also set as outcomes to further analyze the impact of BMI on them. Main outcome measures BMI and obesity were treated as the outcomes to evaluate the effect of serum TSH on them, and TSH was set as the outcome to estimate the effect of BMI and obesity on it. Results Both IVW and MR-Egger results indicated that genetically driven serum TSH did not causally lead to changes in BMI or obesity. Moreover, the IVW method showed that the TSH level could be significantly elevated by genetically predicted high BMI (β=0.038, se=0.013, p=0.004). In further MR analysis, the IVW method indicated that BMI could causally increase the fT3 (β=10.123, se=2.523, p Conclusion Together with fT3, TSH can be significantly elevated by an increase in genetically driven BMI.