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Clinical Endocrinology

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

Authors

  • V. Panicker,

    1. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia,
    2. Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, University of Bristol, Bristol, UK,
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  • S. G. Wilson,

    1. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia,
    2. School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia
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  • T. D. Spector,

    1. Twin Research and Genetic Epidemiology Unit, King's College London, London, UK,
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  • S. J. Brown,

    1. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia,
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  • M. Falchi,

    1. Twin Research and Genetic Epidemiology Unit, King's College London, London, UK,
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  • J. B. Richards,

    1. Twin Research and Genetic Epidemiology Unit, King's College London, London, UK,
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  • G. L. Surdulescu,

    1. Twin Research and Genetic Epidemiology Unit, King's College London, London, UK,
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  • E. M. Lim,

    1. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia,
    2. Pathwest Laboratory Medicine WA, Nedlands, Western Australia, Australia and
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  • S. J. Fletcher,

    1. Pathwest Laboratory Medicine WA, Nedlands, Western Australia, Australia and
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  • J. P. Walsh

    1. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia,
    2. School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia
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Clin A/Prof John P. Walsh, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia. E-mail: john.walsh@health.wa.gov.au

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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