A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents

Tenna Ruest Haarmark Nielsen, Emil Vincent Rosenbaum Appel, Mathilde Svendstrup, Johanne Dam Ohrt, Maria Dahl, Cilius Esmann Fonvig, Mette Hollensted, Christian Theil Have, Haja N. Kadarmideen, Oluf Pedersen, Torben Hansen, Jens-Christian Holm, Niels Grarup, David Meyre (Editor)

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    Abstract

    BackgroundHypothyroidism is associated with obesity, and thyroid hormones are involved in the regulation of body composition, including fat mass. Genome-wide association studies (GWAS) in adults have identified 19 and 6 loci associated with plasma concentrations of thyroid stimulating hormone (TSH) and free thyroxine (fT4), respectively.ObjectiveThis study aimed to identify and characterize genetic variants associated with circulating TSH and fT4 in Danish children and adolescents and to examine whether these variants associate with obesity.MethodsGenome-wide association analyses of imputed genotype data with fasting plasma concentrations of TSH and fT4 from a population-based sample of Danish children, adolescents, and young adults, and a group of children, adolescents, and young adults with overweight and obesity were performed (N = 1,764, mean age = 12.0 years [range 2.5-24.7]). Replication was performed in additional comparable samples (N = 2,097, mean age = 11.8 years [1.2-22.8]). Meta-analyses, using linear additive fixed-effect models, were performed on the results of the discovery and replication analyses.ResultsNo novel loci associated with TSH or fT4 were identified. Four loci previously associated with TSH in adults were confirmed in this study population (PDE10A (rs2983511: beta = 0.112SD, p = 4.8.10(-16)), FOXE1 (rs7847663: beta = 0.223SD, p = 1.5 . 10(-20)), NR3C2 (rs9968300: beta = 0.194SD), p = 2.4 . 10(-11)), VEGFA (rs2396083: beta = 0.088SD, p = 2.2 . 10(-10))). Effect sizes of variants known to associate with TSH or fT4 in adults showed a similar direction of effect in our cohort of children and adolescents, 11 of which were associated with TSH or fT4 in our study (p
    Original languageEnglish
    Article numbere0174204
    JournalP L o S One
    Volume12
    Issue number3
    ISSN1932-6203
    DOIs
    Publication statusPublished - 2017

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    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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    Nielsen, T. R. H., Appel, E. V. R., Svendstrup, M., Ohrt, J. D., Dahl, M., Fonvig, C. E., Hollensted, M., Have, C. T., Kadarmideen, H. N., Pedersen, O., Hansen, T., Holm, J-C., Grarup, N., & Meyre, D. (Ed.) (2017). A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents. P L o S One, 12(3), [e0174204]. https://doi.org/10.1371/journal.pone.0174204