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Thyroid Function and Metabolic Syndrome: A Two-Sample Bidirectional Mendelian Randomization Study.

Nikolina Pleić1, Ivana Gunjača1, Mirjana Babić Leko1

  • 1Department of Medical Biology, University of Split, School of Medicine, Split, 21000  Croatia.

The Journal of Clinical Endocrinology and Metabolism
|June 20, 2023
PubMed
Summary

Higher free thyroxine (fT4) levels may reduce the risk of metabolic syndrome (MetS). Additionally, high-density lipoprotein cholesterol (HDL-C) appears to influence thyroid-stimulating hormone (TSH) levels, suggesting a bidirectional relationship.

Keywords:
Mendelian randomization analysismetabolic syndromethyroid gland

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Area of Science:

  • Endocrinology and Metabolism
  • Genetics and Genomics
  • Cardiovascular Health

Background:

  • Observational studies suggest a link between thyroid function and metabolic syndrome (MetS).
  • The causal direction and mechanisms underlying this association remain unclear.
  • Investigating genetic links can elucidate these relationships.

Purpose of the Study:

  • To determine the genetically predicted causal effects of thyroid function on MetS risk.
  • To examine the reverse causality: effects of MetS components on thyroid function.
  • To utilize large-scale genetic association data for robust analysis.

Main Methods:

  • Two-sample bidirectional Mendelian randomization (MR) study.
  • Utilized summary statistics from comprehensive genome-wide association studies (GWAS).
  • Analyzed thyroid-stimulating hormone (TSH), free thyroxine (fT4), MetS, and its components (waist circumference, fasting blood glucose, hypertension, triglycerides, HDL-C).

Main Results:

  • Higher genetically predicted free thyroxine (fT4) was associated with reduced MetS risk (OR = 0.96, P = .037).
  • fT4 positively correlated with high-density lipoprotein cholesterol (HDL-C) (β = 0.02, P = .008).
  • Genetically predicted HDL-C showed a negative association with TSH (β = -0.03, P = .046).

Conclusions:

  • Normal-range thyroid function variations are causally linked to MetS diagnosis and lipid profiles.
  • High-density lipoprotein cholesterol (HDL-C) may have a causal effect on thyroid-stimulating hormone (TSH) levels.
  • Findings support a bidirectional relationship between thyroid function and metabolic health.