Genetic determinants of thyroid function in children

Tessa A. Mulder, Purdey J. Campbell, Peter N. Taylor, Robin P. Peeters, Scott G. Wilson, Marco Medici, Colin Dayan, Vincent V.W. Jaddoe, John P. Walsh, Nicholas G. Martin, Henning Tiemeier, Tim I.M. Korevaar*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Downloads (Pure)

Abstract

OBJECTIVE:

Genome-wide association studies in adults have identified 42 loci associated with thyroid stimulating hormone (TSH) and 21 loci associated with free thyroxine (FT4) concentrations. While biologically plausible, age-dependent effects have not been assessed. We aimed to study the association of previously identified genetic determinants of TSH and FT4 with TSH and FT4 concentrations in newborns and (pre)school children. 

METHODS: 

We selected participants from three population-based prospective cohorts with data on genetic variants and thyroid function: Generation R (N = 2169 children, mean age 6 years; N = 2388 neonates, the Netherlands), the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3382, age 7.5 years, United Kingdom), and the Brisbane Longitudinal Twin Study (BLTS; N = 1680, age 12.1 years, Australia). The association of single nucleotide polymorphisms (SNPs) with TSH and FT4 concentrations was studied with multivariable linear regression models. Weighted polygenic risk scores (PRSs) were defined to combine SNP effects.

RESULTS:

In childhood, 30/60 SNPs were associated with TSH and 11/31 SNPs with FT4 after multiple testing correction. The effect sizes for AADAT, GLIS3, TM4SF4, and VEGFA were notably larger than in adults. The TSH PRS explained 5.3%-8.4% of the variability in TSH concentrations; the FT4 PRS explained 1.5%-4.2% of the variability in FT4 concentrations. Five TSH SNPs and no FT4 SNPs were associated with thyroid function in neonates. 

CONCLUSIONS: 

The effects of many known thyroid function SNPs are already apparent in childhood and some might be notably larger in children as compared to adults. These findings provide new knowledge about genetic regulation of thyroid function in early life.

Original languageEnglish
Pages (from-to)164-174
Number of pages11
JournalEuropean Journal of Endocrinology
Volume189
Issue number2
DOIs
Publication statusPublished - Aug 2023

Bibliographical note

Publisher Copyright:
© The Author(s) 2023. Published by Oxford University.

Fingerprint

Dive into the research topics of 'Genetic determinants of thyroid function in children'. Together they form a unique fingerprint.

Cite this