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

V. Panicker, Scott Wilson, T.D. Spector, S.J. Brown, M. Falchi, J.B. Richards, G.L. Surdulexcu, Ee Lim, S.J. Fletcher, John Walsh

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Abstract

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 x 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 x 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 x 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.
Original languageEnglish
Pages (from-to)652-659
JournalClinical Endocrinology
Volume68
Issue number4
DOIs
Publication statusPublished - 2008

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Thyroid Gland
Serum
Thyroid Hormones
Registries
Smoking
Confidence Intervals
Antibodies
Genes

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Panicker, V. ; Wilson, Scott ; Spector, T.D. ; Brown, S.J. ; Falchi, M. ; Richards, J.B. ; Surdulexcu, G.L. ; Lim, Ee ; Fletcher, S.J. ; Walsh, John. / Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort. In: Clinical Endocrinology. 2008 ; Vol. 68, No. 4. pp. 652-659.
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abstract = "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 x 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 x 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 x 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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Panicker, V, Wilson, S, Spector, TD, Brown, SJ, Falchi, M, Richards, JB, Surdulexcu, GL, Lim, E, Fletcher, SJ & Walsh, J 2008, 'Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort' Clinical Endocrinology, vol. 68, no. 4, pp. 652-659. https://doi.org/10.1111/j.1365-2265.2007.03079.x

Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort. / Panicker, V.; Wilson, Scott; Spector, T.D.; Brown, S.J.; Falchi, M.; Richards, J.B.; Surdulexcu, G.L.; Lim, Ee; Fletcher, S.J.; Walsh, John.

In: Clinical Endocrinology, Vol. 68, No. 4, 2008, p. 652-659.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort

AU - Panicker, V.

AU - Wilson, Scott

AU - Spector, T.D.

AU - Brown, S.J.

AU - Falchi, M.

AU - Richards, J.B.

AU - Surdulexcu, G.L.

AU - Lim, Ee

AU - Fletcher, S.J.

AU - Walsh, John

PY - 2008

Y1 - 2008

N2 - 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 x 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 x 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 x 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.

AB - 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 x 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 x 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 x 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.

U2 - 10.1111/j.1365-2265.2007.03079.x

DO - 10.1111/j.1365-2265.2007.03079.x

M3 - Article

VL - 68

SP - 652

EP - 659

JO - Clinical Endocrinology

JF - Clinical Endocrinology

SN - 0300-0664

IS - 4

ER -