A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.

Details

Serval ID
serval:BIB_3649986D469A
Type
Article: article from journal or magazin.
Collection
Publications
Title
A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.
Journal
PLoS genetics
Author(s)
Porcu E., Medici M., Pistis G., Volpato C.B., Wilson S.G., Cappola A.R., Bos S.D., Deelen J., den Heijer M., Freathy R.M., Lahti J., Liu C., Lopez L.M., Nolte I.M., O'Connell J.R., Tanaka T., Trompet S., Arnold A., Bandinelli S., Beekman M., Böhringer S., Brown S.J., Buckley B.M., Camaschella C., de Craen A.J., Davies G., de Visser M.C., Ford I., Forsen T., Frayling T.M., Fugazzola L., Gögele M., Hattersley A.T., Hermus A.R., Hofman A., Houwing-Duistermaat J.J., Jensen R.A., Kajantie E., Kloppenburg M., Lim E.M., Masciullo C., Mariotti S., Minelli C., Mitchell B.D., Nagaraja R., Netea-Maier R.T., Palotie A., Persani L., Piras M.G., Psaty B.M., Räikkönen K., Richards J.B., Rivadeneira F., Sala C., Sabra M.M., Sattar N., Shields B.M., Soranzo N., Starr J.M., Stott D.J., Sweep F.C., Usala G., van der Klauw M.M., van Heemst D., van Mullem A., Vermeulen S.H., Visser W.E., Walsh J.P., Westendorp R.G., Widen E., Zhai G., Cucca F., Deary I.J., Eriksson J.G., Ferrucci L., Fox C.S., Jukema J.W., Kiemeney L.A., Pramstaller P.P., Schlessinger D., Shuldiner A.R., Slagboom E.P., Uitterlinden A.G., Vaidya B., Visser T.J., Wolffenbuttel B.H., Meulenbelt I., Rotter J.I., Spector T.D., Hicks A.A., Toniolo D., Sanna S., Peeters R.P., Naitza S.
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
9
Number
2
Pages
e1003266
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Abstract
Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.
Keywords
Female, Genome-Wide Association Study, Humans, Hyperthyroidism/blood, Hyperthyroidism/genetics, Hypothyroidism/blood, Hypothyroidism/genetics, Male, Phenotype, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Sex Characteristics, Signal Transduction/genetics, Thyroid Gland/metabolism, Thyroid Gland/physiopathology, Thyrotropin/blood, Thyrotropin/genetics, Thyroxine/blood, Thyroxine/genetics
Pubmed
Web of science
Open Access
Yes
Create date
18/01/2021 22:45
Last modification date
19/01/2021 7:26
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