Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort

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.

doi:10.1111/j.1365-2265.2007.03079.x

Cited by 128Thyroid Disorders and TreatmentsGenetic Associations and EpidemiologyThyroid Cancer Diagnosis and Treatment

Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort

Panicker, V., Wilson, S. G., Spector, T. D., Brown, S. J., Falchi, M., Richards, J. B., Surdulescu, G. L., Lim, E. M. +2 more·2008·Clinical Endocrinology

DOI 10.1111/j.1365-2265.2007.03079.x

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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 a large cohort of twin pairs, TTSI was strongly influenced by genetic factors.
“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]
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”
From Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status (2023) · cites this paper as [109]
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.”
From Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status (2023) · cites this paper as [109]
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.”
From Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status (2023) · cites this paper as [109]
Thyroid hormone levels are largely genetically determined, with similar genetic effects observed in children and adults.
“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]

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“In a large cohort of twin pairs TTSIwas strongly influenced by genetic factors (77).”
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Hereditary and Environmental Influences on the Variation of Thyroid Hormones in Normal Male Twins*
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Major Genetic Influence on the Regulation of the Pituitary-Thyroid Axis: A Study of Healthy Danish Twins
Hansen, P. S., Brix, T. H., Sørensen, T. I. A., Kyvik, K. O., & Hegedüs, L. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031641 · Cited by 257 · see citing works
Genetic and environmental interrelations between measurements of thyroid function in a healthy Danish twin population
Hansen, P. S., Brix, T. H., Iachine, I., Sørensen, T. I. A., Kyvik, K. O., & Hegedüs, L. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00321.2006 · Cited by 43 · see citing works
Genome-wide analysis of thyroid function in Australian adolescents highlights SERPINA7 and NCOA3
Nolan, J. D., Campbell, P. J., Brown, S. J., Zhu, G., Gordon, S. D., Lim, E. M., McGrath, J. J., Cross, S., Panicker, V., Medland, S. E., et al. (2021) · European Journal of Endocrinology · doi:10.1530/eje-21-0614 · Cited by 6 · see citing works
Self-citation
Genetic and Environmental Causes of Individual Differences in Thyroid Size: A Study of Healthy Danish Twins
Hansen, P. S., Brix, T. H., Bennedbæk, F. N., Bonnema, S. J., Kyvik, K. O., & Hegedűs, L. D. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031999 · Cited by 91 · see citing works

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: Panicker, V.
Wilson, S. G.
Spector, T. D.
Brown, S. J.
Falchi, M.
Richards, J. B.
Lim, E. M.
Walsh, J. P.
Venue: Clinical Endocrinology
Publisher: Wiley
Published: 2007-09-19
Volume: 68
Issue: 4
Pages: 652-659
ISSN: 0300-0664 (ISSN-L)
1365-2265
DOI: 10.1111/j.1365-2265.2007.03079.x
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort

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