Variation in Normal Range Thyroid Function Affects Serum Cholesterol Levels, Blood Pressure, and Type 2 Diabetes...

Area of Science:

• Endocrinology
• Cardiovascular Genetics
• Metabolic Diseases

Background:

• Observational studies link normal-range thyroid function to cardiovascular risk factors like dyslipidemia, hypertension, type 2 diabetes (T2D), and obesity.
• Limitations of observational studies include confounding, reverse causality, and selection bias.
• Mendelian randomization (MR) is employed to assess causality.

Purpose of the Study:

• To investigate the causal relationship between normal-range thyroid function (thyrotropin [TSH] and free thyroxine [fT4] levels) and major cardiovascular risk factors.
• To differentiate causal effects from observational associations.

Main Methods:

• Utilized a two-sample Mendelian randomization (MR) approach.
• Employed large-scale genome-wide association study (GWAS) data for TSH, fT4, lipid levels, blood pressure, T2D, and obesity traits (BMI, waist/hip ratio).

Main Results:

• A one SD increase in genetically predicted TSH levels was associated with increased total cholesterol (0.037 SD) and low-density lipoprotein (0.026 SD) levels.
• TSH levels showed a significant inverse association with pulse pressure (-0.477 mmHg) and T2D risk (OR=0.95).
• No causal link was found between TSH/fT4 and obesity, but increased BMI causally reduced fT4 levels (-0.075 SD).

Conclusions:

• Normal-range thyroid function variation causally affects serum cholesterol levels, blood pressure, and T2D risk.
• Genetically predicted BMI influences fT4 levels, suggesting a bidirectional relationship.
• MR analysis provides robust evidence for thyroid function's role in cardiovascular risk.