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

doi:10.1371/journal.pone.0174204

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)

Research output: Contribution to journal › Journal article › Research › peer-review

399 Downloads (Pure)

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 language	English
Article number	e0174204
Journal	P L o S One
Volume	12
Issue number	3
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0174204
Publication status	Published - 2017

Bibliographical note

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1371/journal.pone.0174204

JournalFinal published version, 2.24 MB

OpenUrl availability

Full text

Cite this

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), Article e0174204. https://doi.org/10.1371/journal.pone.0174204

@article{6592d98c48b643929308f24b25fe6ffb,

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

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",

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

note = "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",

year = "2017",

doi = "10.1371/journal.pone.0174204",

language = "English",

volume = "12",

journal = "P L o S One",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "3",

}

Nielsen, TRH, Appel, EVR, Svendstrup, M, Ohrt, JD, Dahl, M, Fonvig, CE, Hollensted, M, Have, CT, Kadarmideen, HN, 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, vol. 12, no. 3, e0174204. https://doi.org/10.1371/journal.pone.0174204

TY - JOUR

T1 - A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents

AU - Nielsen, Tenna Ruest Haarmark

AU - Appel, Emil Vincent Rosenbaum

AU - Svendstrup, Mathilde

AU - Ohrt, Johanne Dam

AU - Dahl, Maria

AU - Fonvig, Cilius Esmann

AU - Hollensted, Mette

AU - Have, Christian Theil

AU - Kadarmideen, Haja N.

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Holm, Jens-Christian

AU - Grarup, Niels

A2 - Meyre, David

N1 - 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

PY - 2017

Y1 - 2017

N2 - 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

AB - 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

U2 - 10.1371/journal.pone.0174204

DO - 10.1371/journal.pone.0174204

M3 - Journal article

C2 - 28333968

SN - 1932-6203

VL - 12

JO - P L o S One

JF - P L o S One

IS - 3

M1 - e0174204

ER -

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

Abstract

Bibliographical note

UN SDGs

Access to Document

OpenUrl availability

Fingerprint

Cite this