Genetic Loci Linked to Pituitary-Thyroid Axis Set Points : A Genome-Wide Scan of a Large Twin Cohort

V. Panicker, Scott Wilson, T.D. Spector, S.J. Brown, B.S. Kato, P.W. Reed, M. Falchi, B. Richards, L. Surdulescu, Ee Lim, S.J. Fletcher, John Walsh

Research output: Contribution to journalArticle

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Abstract

Objective: Previous studies have shown that circulating concentrations of TSH, free T-4, and free T-3 are genetically regulated, but the genes responsible remain largely unknown. The aim of this study was to identify genetic loci associated with these parameters.Design: We performed a multipoint, nonparametric genome-wide linkage scan of 613 female dizygotic twin pairs. All subjects were euthyroid (TSH 0.4-4.0 mU/liter) with negative thyroid peroxidase antibodies and no history of thyroid disease. The genome scan comprised 737 microsatellite markers supplemented with dinucleotide markers. Data were analyzed using residualized thyroid hormone data after adjustment for age, smoking, and body mass index.Results: Multipoint linkage analysis gave linkage peaks for free T-4 on chromosome 14q13 and 18q21 [logarithm of odds (LOD) 2.4-3.2]; TSH on chromosomes 2q36, 4q32, and 9q34 (LOD 2.1-3.2); and free T3 on chromosomes 7q36, 8q22, and 18q21 (LOD 2.0-2.3).Conclusions: This study has identified eight genomiclocations with linkage of LOD of 2.0 or greater. These results should enable targeted positional candidate and positional cloning studies to advance our understanding of genetic control of the pituitary-thyroid axis.
Original languageEnglish
Pages (from-to)3519-3523
JournalJournal of Clinical Endocrinology and Metabolism
Volume93
Issue number9
DOIs
Publication statusPublished - 2008

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Genetic Loci
Chromosomes
Thyroid Gland
Genes
Genome
Dizygotic Twins
Iodide Peroxidase
Chromosomes, Human, Pair 4
Thyroid Diseases
Thyroid Hormones
Microsatellite Repeats
Organism Cloning
Body Mass Index
Research Design
Cloning
Smoking
Antibodies

Cite this

Panicker, V. ; Wilson, Scott ; Spector, T.D. ; Brown, S.J. ; Kato, B.S. ; Reed, P.W. ; Falchi, M. ; Richards, B. ; Surdulescu, L. ; Lim, Ee ; Fletcher, S.J. ; Walsh, John. / Genetic Loci Linked to Pituitary-Thyroid Axis Set Points : A Genome-Wide Scan of a Large Twin Cohort. In: Journal of Clinical Endocrinology and Metabolism. 2008 ; Vol. 93, No. 9. pp. 3519-3523.
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Panicker, V, Wilson, S, Spector, TD, Brown, SJ, Kato, BS, Reed, PW, Falchi, M, Richards, B, Surdulescu, L, Lim, E, Fletcher, SJ & Walsh, J 2008, 'Genetic Loci Linked to Pituitary-Thyroid Axis Set Points : A Genome-Wide Scan of a Large Twin Cohort' Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 9, pp. 3519-3523. https://doi.org/10.1210/jc.2007-2650

Genetic Loci Linked to Pituitary-Thyroid Axis Set Points : A Genome-Wide Scan of a Large Twin Cohort. / Panicker, V.; Wilson, Scott; Spector, T.D.; Brown, S.J.; Kato, B.S.; Reed, P.W.; Falchi, M.; Richards, B.; Surdulescu, L.; Lim, Ee; Fletcher, S.J.; Walsh, John.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 93, No. 9, 2008, p. 3519-3523.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic Loci Linked to Pituitary-Thyroid Axis Set Points : A Genome-Wide Scan of a Large Twin Cohort

AU - Panicker, V.

AU - Wilson, Scott

AU - Spector, T.D.

AU - Brown, S.J.

AU - Kato, B.S.

AU - Reed, P.W.

AU - Falchi, M.

AU - Richards, B.

AU - Surdulescu, L.

AU - Lim, Ee

AU - Fletcher, S.J.

AU - Walsh, John

PY - 2008

Y1 - 2008

N2 - Objective: Previous studies have shown that circulating concentrations of TSH, free T-4, and free T-3 are genetically regulated, but the genes responsible remain largely unknown. The aim of this study was to identify genetic loci associated with these parameters.Design: We performed a multipoint, nonparametric genome-wide linkage scan of 613 female dizygotic twin pairs. All subjects were euthyroid (TSH 0.4-4.0 mU/liter) with negative thyroid peroxidase antibodies and no history of thyroid disease. The genome scan comprised 737 microsatellite markers supplemented with dinucleotide markers. Data were analyzed using residualized thyroid hormone data after adjustment for age, smoking, and body mass index.Results: Multipoint linkage analysis gave linkage peaks for free T-4 on chromosome 14q13 and 18q21 [logarithm of odds (LOD) 2.4-3.2]; TSH on chromosomes 2q36, 4q32, and 9q34 (LOD 2.1-3.2); and free T3 on chromosomes 7q36, 8q22, and 18q21 (LOD 2.0-2.3).Conclusions: This study has identified eight genomiclocations with linkage of LOD of 2.0 or greater. These results should enable targeted positional candidate and positional cloning studies to advance our understanding of genetic control of the pituitary-thyroid axis.

AB - Objective: Previous studies have shown that circulating concentrations of TSH, free T-4, and free T-3 are genetically regulated, but the genes responsible remain largely unknown. The aim of this study was to identify genetic loci associated with these parameters.Design: We performed a multipoint, nonparametric genome-wide linkage scan of 613 female dizygotic twin pairs. All subjects were euthyroid (TSH 0.4-4.0 mU/liter) with negative thyroid peroxidase antibodies and no history of thyroid disease. The genome scan comprised 737 microsatellite markers supplemented with dinucleotide markers. Data were analyzed using residualized thyroid hormone data after adjustment for age, smoking, and body mass index.Results: Multipoint linkage analysis gave linkage peaks for free T-4 on chromosome 14q13 and 18q21 [logarithm of odds (LOD) 2.4-3.2]; TSH on chromosomes 2q36, 4q32, and 9q34 (LOD 2.1-3.2); and free T3 on chromosomes 7q36, 8q22, and 18q21 (LOD 2.0-2.3).Conclusions: This study has identified eight genomiclocations with linkage of LOD of 2.0 or greater. These results should enable targeted positional candidate and positional cloning studies to advance our understanding of genetic control of the pituitary-thyroid axis.

U2 - 10.1210/jc.2007-2650

DO - 10.1210/jc.2007-2650

M3 - Article

VL - 93

SP - 3519

EP - 3523

JO - Journal of Endocrinology & Metabolism

JF - Journal of Endocrinology & Metabolism

SN - 0021-972X

IS - 9

ER -