Genome-wide meta-analysis identifies novel loci associated with free triiodothyronine and thyroid-stimulating hormone.
J Endocrinol Invest
; 42(10): 1171-1180, 2019 Oct.
Article
em En
| MEDLINE
| ID: mdl-30843173
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças da Glândula Tireoide
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Tri-Iodotironina
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Tireotropina
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Estudo de Associação Genômica Ampla
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Loci Gênicos
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Endocrinol Invest
Ano de publicação:
2019
Tipo de documento:
Article