Supplementary data to the paper: 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<0.001) while not significantly affecting the
fT4 level. Conclusion Together with fT3, TSH can be significantly elevated
by an increase in genetically driven BMI.