Dataset Information

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

ABSTRACT:

Background

Hypothyroidism 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.

Objective

This 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.

Methods

Genome-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.

Results

No 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: ? = 0.112SD, p = 4.8 ? 10-16), FOXE1 (rs7847663: ? = 0.223SD, p = 1.5 ? 10-20), NR3C2 (rs9968300: ? = 0.194SD), p = 2.4 ? 10-11), VEGFA (rs2396083: ? = 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<0.0002). None of the TSH or fT4 associated SNPs were associated with obesity in our cohort, indicating no pleiotropic effects of these variants on obesity.

Conclusion

In a group of Danish children and adolescents, four loci previously associated with plasma TSH concentrations in adults, were associated with plasma TSH concentrations in children, suggesting comparable genetic determinants of thyroid function in adults and children.

SUBMITTER: Nielsen TR

PROVIDER: S-EPMC5363901 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

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

Nielsen Tenna Ruest Haarmark TR Appel Emil Vincent Rosenbaum EV Svendstrup Mathilde M Ohrt Johanne Dam JD Dahl Maria M Fonvig Cilius Esmann CE Hollensted Mette M Have Christian Theil CT Kadarmideen Haja N HN Pedersen Oluf O Hansen Torben T Holm Jens-Christian JC Grarup Niels N

PloS one 20170323 3

<h4>Background</h4>Hypothyroidism 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.<h4>Objective</h4>This study aimed to identify and characterize genetic variants associated with circulating TSH and fT4 in Danish children and adolesce ...[more]

PMID: 28333968

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Project description:IntroductionLittle is known about the pathophysiology of hyperemesis gravidarum (HG). Proposed underlying causes are multifactorial and thyroid function is hypothesized to be causally involved. In this study, we aimed to assess the utility of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) as a marker and predictor for the severity and clinical course of HG.Material and methodsWe conducted a prospective cohort study including women admitted for HG between 5 and 20 weeks of gestation in 19 hospitals in the Netherlands. Women with a medical history of thyroid disease were excluded. TSH and FT4 were measured at study entry. To adjust for gestational age, we calculated TSH multiples of the median (MoM). We assessed HG severity at study entry as severity of nausea and vomiting (by the Pregnancy Unique Quantification of Emesis and nausea score), weight change compared with prepregnancy weight, and quality of life. We assessed the clinical course of HG as severity of nausea and vomiting and quality of life 1 week after inclusion, duration of hospital admissions, and readmissions. We performed multivariable regression analysis with absolute TSH, TSH MoMs, and FT4.ResultsBetween 2013 and 2016, 215 women participated in the cohort. TSH, TSH MoM, and FT4 were available for, respectively, 150, 126, and 106 of these women. Multivariable linear regression analysis showed that lower TSH MoM was significantly associated with increased weight loss or lower weight gain at study entry (ΔKg; β = 2.00, 95% CI 0.47-3.53), whereas absolute TSH and FT4 were not. Lower TSH, not lower TSH MoM or FT4, was significantly associated with lower nausea and vomiting scores 1 week after inclusion (β = 1.74, 95% CI 0.36-3.11). TSH and FT4 showed no association with any of the other markers of the severity or clinical course of HG. Twenty-one out of 215 (9.8%) women had gestational transient thyrotoxicosis. Women with gestational transient thyrotoxicosis had a lower quality of life 1 week after inclusion than women with no gestational transient thyrotoxicosis (p = 0.03).ConclusionsOur findings show an inconsistent role for TSH, TSH MoM, or FT4 at time of admission and provide little guidance on the severity and clinical course of HG.

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Dataset Information

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

Background

Objective

Methods

Results

Conclusion

Publications

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

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