Genetic and environmental interrelations between measurements of thyroid function in a healthy Danish twin population
Abstract
Serum thyrotropin (TSH), free thyroxine (T 4), and free triiodothyronine (T 3) levels illustrate the thyroid function set point, but the interrelations between these have never been characterized in detail. The aim of this study was to examine the associations between TSH and thyroid hormone levels in healthy euthyroid twins and to determine the extent to which the same genes influence more than one of these biochemical traits; 1,380 healthy euthyroid Danish twins (284 monozygotic, 286 dizygotic, 120 opposite-sex twin pairs) were recruited. Genetic and environmental associations between thyroid function measurements were examined using quantitative genetic modeling. In bivariate genetic models, the phenotypic relation between two measurements was divided into genetic and environmental correlations. Free T 4 and free T 3 levels were positively correlated ( r = 0.32, P < 0.0001). The genetic correlation between serum free T 4 and free T 3 levels was r g = 0.25 (95% CI 0.14–0.35), suggesting that a set of common genes affect both phenotypes (pleiotropy). The correlation between the environmental effects was r e = 0.41 (0.32–0.50). From this we calculated that the proportion of the correlation between free T 4 and free T 3 levels mediated by common genetic factors was 48%. Only 7% of the genetic component of serum free T 3 levels is shared with serum free T 4. Serum TSH and thyroid hormone levels did not share any genetic influences. In conclusion, thyroid hormone levels are partly genetically correlated genes that affect free T 4 levels and exert pleiotropic effects on free T 3 levels, although most of the genetic variance for these measurements is trait specific.
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Population-based reference intervals for thyroid test variables are much broader than the narrow within-subject variance and consequently are less useful for monitoring an individual patient.
“Population-based reference intervals for thyroid test variables are, therefore, much broader than the rather narrow within-subject variance and consequently are less useful for monitoring an individual patient.108–113”
Heritability accounts for 30% to 65% of the variance in TSH, fT4, fT3, and the fT4 × TSH product.
“Such studies reveal that heritability accounts for 30% to 65% of the variance in TSH, fT4, fT3, and the fT4 × TSH product.”
Systematic studies in healthy mono- and dizygotic twins, repetitive sampling studies, and testing of individuals or subpopulations in different regions have shown markedly narrower within-subject variability than between-subject variations.
“Results from systematic studies in healthy mono- and dizygotic twins, repetitive sampling studies, and the testing of individuals or (sub-)populations in different regions have shown markedly narrower within-subject variability (e.g., during monthly sampling) than between-subject variations.”
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- Authors
- Hansen, P. S., Brix, T. H., Iachine, I., Sørensen, T. I. A., Kyvik, K. O., & Hegedüs, L.
- Affiliations
- Odense University Hospital (DK)
- University of Copenhagen (DK)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2007-03
- Volume
- 292
- Issue
- 3
- Pages
- E765-E770
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2128257531
- Cited by
- 43
- References
- 22
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 1 · 2022: 1 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 1 · 2015: 1 · 2014: 2 · 2013: 7
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- thyroid function, thyroid-stimulating hormone, free thyroxine, free triiodothyronine, genetic correlation, environmental correlation, pleiotropy, thyroid hormone levels, heritability
- MeSH terms
- Adult, Denmark, Environment, Female, Genotype, Humans, Male, Middle Aged, Models, Genetic, Phenotype, Thyroid Gland, Thyroid Hormones, Thyrotropin, Twins, Dizygotic, Twins, Monozygotic
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