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Functions of Thyroid Hormones01:18

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The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
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Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
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Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
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The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
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Genetic determinants of thyroid function in children.

Tessa A Mulder1,2,3, Purdey J Campbell4, Peter N Taylor5

  • 1Generation R Study Group, Erasmus University Medical Center, Rotterdam, CA 3000, The Netherlands.

European Journal of Endocrinology
|August 2, 2023
PubMed
Summary
This summary is machine-generated.

Genetic factors influencing thyroid stimulating hormone (TSH) and free thyroxine (FT4) are present in childhood, with some effects being larger than in adults. This study reveals early-life genetic regulation of thyroid function.

Keywords:
childhoodgenetic risk scoregenetic variantsthyroid function

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Area of Science:

  • Endocrinology
  • Genetics
  • Pediatrics

Background:

  • Genome-wide association studies have identified numerous genetic loci linked to thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations in adults.
  • The age-dependent effects of these genetic determinants on thyroid function have not been thoroughly investigated.

Purpose of the Study:

  • To investigate the association of previously identified genetic determinants of TSH and FT4 with these hormone concentrations in newborns and children.
  • To assess potential age-dependent variations in the effects of genetic variants on thyroid function.

Main Methods:

  • Utilized data from three prospective population-based cohorts: Generation R, Avon Longitudinal Study of Parents and Children (ALSPAC), and Brisbane Longitudinal Twin Study (BLTS).
  • Analyzed associations between single nucleotide polymorphisms (SNPs) and TSH/FT4 concentrations using multivariable linear regression.
  • Constructed weighted polygenic risk scores (PRSs) to aggregate SNP effects.

Main Results:

  • In childhood, a significant proportion of SNPs (30/60 for TSH, 11/31 for FT4) showed associations with thyroid function after multiple testing correction.
  • Effect sizes for specific genes (AADAT, GLIS3, TM4SF4, VEGFA) were notably larger in children compared to adults.
  • TSH and FT4 PRSs explained a considerable portion of variability in concentrations (5.3%-8.4% for TSH, 1.5%-4.2% for FT4).
  • Five TSH-associated SNPs demonstrated associations in neonates, while no FT4-associated SNPs were found in this age group.

Conclusions:

  • Many known genetic variants affecting thyroid function are already active in childhood.
  • The impact of certain genetic determinants on thyroid hormones may be more pronounced in children than in adults.
  • These findings contribute novel insights into the genetic regulation of thyroid function during early development.