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

Objective: Previous studies have shown that circulating concentrations of TSH, free T4, and free T3 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, non...

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Published in:The journal of clinical endocrinology and metabolism 2008-09, Vol.93 (9), p.3519-3523
Main Authors: Panicker, Vijay, Wilson, Scott G., Spector, Tim D., Brown, Suzanne J., Kato, Bernet S., Reed, Peter W., Falchi, Mario, Richards, J. Brent, Surdulescu, Gabriela L., Lim, Ee M., Fletcher, Steven J., Walsh, John P.
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Chromosome Mapping
Chromosomes, Human
Cohort Studies
Endocrinopathies
Feeding. Feeding behavior
Female
Fundamental and applied biological sciences. Psychology
Genetic Linkage
Genome, Human
Humans
Lod Score
Medical sciences
Middle Aged
Pituitary Gland - physiology
Quantitative Trait Loci
Thyroid Gland - physiology
Thyrotropin - blood
Thyrotropin - genetics
Thyroxine - blood
Thyroxine - genetics
Triiodothyronine - blood
Triiodothyronine - genetics
Twins, Dizygotic - genetics
Twins, Dizygotic - physiology
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Vertebrates: endocrinology
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Summary:Objective: Previous studies have shown that circulating concentrations of TSH, free T4, and free T3 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 T4 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 genomic locations 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.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2007-2650