The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort
Abstract
Summary: Objective Thyroid hormone action influences many metabolic and synthetic processes, but the degree of regulation attributed to genes and environmental factors affecting normal variation remains controversial. Design We investigated the magnitude of the genetic and environmental determination of serum concentrations of free (f) T3, fT4, TSH and the fT4 × TSH product and their variation, in a large cohort of twin pairs. Female dizygous and monozygous twins (849 and 213 pairs, respectively) from the TwinsUK registry (mean age 45·5, range 18–80 years) were studied. Results Comparison of thyroid parameters within various groups showed no differences between smoking categories, and higher serum TSH and lower fT3 in subjects with positive thyroid antibodies. Using structural equation modelling, we estimated the heritable contribution to serum thyroid parameters (with 95% confidence intervals) to be 65% (58%–71%) for TSH, 65% (58%–71%) for the fT4 × TSH product, 39% (20%–55%) for fT4 and 23% (3%–41%) for fT3. Conclusions We conclude that genetic regulation is a particularly important determinant of TSH and the fT4 × TSH product, and is a less important determinant of fT4 and fT3 concentrations in Caucasian women. These data from a large well‐characterized cohort suggest that while there is a strong heritable contribution to serum TSH, variation in fT4 and fT3 concentrations may be less explained by genetic factors and more driven by environmental effects than previously thought.
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In the citing paper
“In a large cohort of twin pairs TTSI was strongly influenced by genetic factors (77).”
From Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research (2016) · cites this paper as [77]
In the citing paper
“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”
In the citing paper
“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.”
In the citing paper
“Such studies reveal that heritability accounts for 30% to 65% of the variance in TSH, fT4, fT3, and the fT4 × TSH product.”
In the citing paper
“Furthermore, thyroid hormone levels are largely genetically determined [6–8] with similar genetic effects observed in children and adults [8].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [6]
In the citing paper
“Regarding genetic factors, up to 67% of the circulating TSH and thyroid hormone concentrations are genetically determined [6] and several candidate genes have been implicated including the genes for phosphodiesterase 8B, DIO1, and the TSH receptor [96].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [6]
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Metadata
- Authors
- Panicker, V., Wilson, S. G., Spector, T. D., Brown, S. J., Falchi, M., Richards, J. B., Surdulescu, G. L., Lim, E. M., Fletcher, S. J., & Walsh, J. P.
- Affiliations
- Sir Charles Gairdner Hospital (AU)
- The University of Western Australia (AU)
- King's College London (GB)
- Pathwest Laboratory Medicine (AU)
- Corresponding author
- Walsh, J. P.
- ORCID
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2007-09-19
- Volume
- 68
- Issue
- 4
- Pages
- 652-659
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W1995092017
- Cited by
- 128
- References
- 46
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 11 · 2023: 13 · 2022: 7 · 2021: 8 · 2020: 4 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 2 · 2013: 10 · 2012: 8
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust
- Abbott Diagnostics
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- heritability, thyroid-stimulating hormone, free thyroxine, free triiodothyronine, thyroid hormones, genetic versus environmental effects, dizygotic twins, monozygotic twins, thyroid autoantibodies, smoking, thyroid function
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Female, United Kingdom, Humans, Male, Middle Aged, Pituitary Gland, Thyroid Gland, Thyrotropin, Thyroxine, Triiodothyronine, Twins, Dizygotic, Twins, Monozygotic
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