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Related Experiment Video

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Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model
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Genetically predicted selenium concentrations and thyroid function: A two-sample Mendelian randomization study.

Hui-Jun Huang1, Shan-Shan Wang1, Ming-Min Jin1

  • 1Department of Epidemiology and Health Statistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Clinical Endocrinology
|December 20, 2022
PubMed
Summary

Selenium (Se) concentration may decrease free thyroxine (FT4) levels, particularly in women. This Mendelian randomization study suggests a potential causal link between higher Se and lower FT4, impacting thyroid function.

Keywords:
Mendelian randomizationseleniumthyroid function

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Area of Science:

  • Endocrinology
  • Nutritional Science
  • Genetics

Background:

  • The relationship between selenium (Se) and human thyroid function is not well understood, with conflicting findings from observational studies.
  • Epidemiological studies are susceptible to bias from confounding factors and reverse causation.
  • Mendelian randomization (MR) offers a method to estimate causal effects by minimizing environmental and lifestyle biases.

Purpose of the Study:

  • To investigate the causal association between selenium concentrations and human thyroid function using a two-sample Mendelian randomization analysis.
  • To leverage genetic variants as instrumental variables for selenium levels to infer causality.
  • To examine sex-specific effects of selenium on thyroid function.

Main Methods:

  • Utilized genome-wide association study (GWAS) data to identify genetic instruments for toenail and blood (TAB) selenium concentrations.
  • Downloaded GWAS summary statistics for thyroid phenotypes including TSH, FT4, hypothyroidism, and hyperthyroidism from the ThyroidOmics consortium.
  • Employed the inverse-variance weighted (IVW) method for primary analysis, supplemented by weighted median and mode-based methods for sensitivity analyses.

Main Results:

  • Genetically determined TAB selenium showed a significant negative association with free thyroxine (FT4) levels (β = -0.067, p = 0.001).
  • A suggestive inverse causal association was found between higher TAB selenium and reduced risk of hypothyroidism (OR = 0.847, p = 0.031).
  • The effect of TAB selenium on FT4 was more pronounced in women (β = -0.076, p = 0.004), indicating sex-specific effects. No significant associations were observed for TSH or hyperthyroidism.

Conclusions:

  • Higher selenium concentrations are causally associated with decreased FT4 levels.
  • The impact of selenium on FT4 levels demonstrates a sex-specific pattern.
  • Mendelian randomization provides robust evidence for the effects of selenium on thyroid hormone levels, addressing limitations of previous studies.