Causal Association Between Serum Thyrotropin and Obesity: A Bidirectional, Mendelian Randomization Study

Area of Science:

• Endocrinology
• Genetics
• Epidemiology

Background:

• The relationship between serum thyrotropin (TSH) and obesity traits like body mass index (BMI) is complex.
• Previous epidemiological studies suggest an association, but a definitive causal link remains unestablished.

Purpose of the Study:

• To investigate the causal association between serum TSH levels and obesity-related traits (BMI and obesity).
• To explore the potential causal effect of BMI and obesity on TSH levels.

Main Methods:

• Utilized bidirectional 2-sample Mendelian randomization (MR) analysis.
• Employed genome-wide association study (GWAS) data for TSH, BMI, and obesity.
• Applied inverse variance-weighted (IVW) and MR-Egger methods for robust causal inference.

Main Results:

• Genetically predicted serum TSH did not demonstrate a causal effect on BMI or obesity.
• A significant causal effect was observed where higher genetically predicted BMI led to elevated TSH levels.
• Increased BMI was also found to causally increase free triiodothyronine (fT3) levels, but not free thyroxine (fT4).

Conclusions:

• Serum TSH is not a causal factor for obesity or BMI.
• Genetically driven increases in BMI can causally elevate both TSH and fT3 levels, suggesting a feedback mechanism.