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Journal of Endocrinological Investigation

Erschienen in:

01.10.2019 | Original Article

Genome-wide meta-analysis identifies novel loci associated with free triiodothyronine and thyroid-stimulating hormone

verfasst von: M. Popović, A. Matana, V. Torlak, T. Boutin, D. Brdar, I. Gunjača, D. Kaličanin, I. Kolčić, V. Boraska Perica, A. Punda, O. Polašek, M. Barbalić, C. Hayward, T. Zemunik

Erschienen in: Journal of Endocrinological Investigation | Ausgabe 10/2019

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Abstract

Purpose

Thyroid hormones are essential for the normal function of almost all human tissues, and have critical roles in metabolism, differentiation and growth. Free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels are under strong genetic influence; however, most of the heritability is yet unexplained.

Methods

In order to identify novel loci associated with fT3, fT4 and TSH serum levels we performed a genome-wide meta-analysis of 7 411 206 polymorphisms in up to 1731 euthyroid individuals from three Croatian cohorts from Dalmatia region: two genetically isolated island populations and one mainland population. Additionally, we also performed a bivariate analysis of fT3 and fT4 levels.

Results

The EPHB2 gene variant rs67142165 reached genome-wide significance for association with fT3 plasma levels (P = 9.27 × 10⁻⁹) and its significance was confirmed in bivariate analysis (P = 9.72 × 10⁻⁹). We also found a genome-wide significant association for variant rs13037502 upstream of the PTPN1 gene and TSH plasma levels (P = 1.67 × 10⁻⁸).

Conclusion

We identified a first genome-wide significant variant associated with fT3 plasma levels, as well as a novel locus associated with TSH plasma levels. These findings are biologically relevant and enrich our knowledge about the genetic basis of pituitary-thyroid axis function.

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Titel: Genome-wide meta-analysis identifies novel loci associated with free triiodothyronine and thyroid-stimulating hormone
verfasst von: M. Popović
A. Matana
V. Torlak
T. Boutin
D. Brdar
I. Gunjača
D. Kaličanin
I. Kolčić
V. Boraska Perica
A. Punda
O. Polašek
M. Barbalić
C. Hayward
T. Zemunik
Publikationsdatum: 01.10.2019
Verlag: Springer International Publishing
Erschienen in: Journal of Endocrinological Investigation / Ausgabe 10/2019
Elektronische ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-019-01030-9

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