Abstract
Background:
Elevations or deficits in thyroid hormone levels are responsible for a wide range of neonatal and adult phenotypes. Several genome-wide, candidate gene, and meta-analysis studies have examined thyroid hormones in adults; however, to our knowledge, no genetic association studies have been performed with neonatal thyroid levels.
Methods:
A population of Iowa neonates, term (n = 827) and preterm (n = 815), were genotyped for 45 single-nucleotide polymorphisms (SNPs). Thyroid-stimulating hormone (TSH) values were obtained from the Iowa Neonatal Metabolic Screening Program. ANOVA was performed to identify genetic associations with TSH concentrations.
Results:
The strongest association was rs4704397 in the PDE8B gene (P = 1.3 × 10−4), followed by rs965513 (P = 6.4 × 10−4) on chromosome 9 upstream of the FOXE1 gene. Both of these SNPs met statistical significance after correction for multiple testing. Six other SNPs were marginally significant (P < 0.05).
Conclusion:
We demonstrated for the first time two genetic associations with neonatal TSH levels that replicate findings with adult TSH levels. These SNPs should be considered early predictors of risk for adult diseases and conditions associated with thyroid hormone levels. Furthermore, this study provides a better understanding of the thyroid profile and potential risk for thyroid disorders in newborns.
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Acknowledgements
We express our thanks to Kim Piper at the Iowa Department of Public Health and the members of the Congenital and Inherited Disorders Advisory Committee for their enthusiastic support and management of this project. We thank Teresa Snell, Franklin Delin, and Dariush Shirazi from the State Hygienic Laboratory for their assistance in the acquisition of the newborn screening data and samples. We thank the families that participated in this study and our research nurse, Laura Knosp, for enrolling families and collecting specimens. We also thank Susan Berends, Tamara Busch, Daniel Cook, Osayame Ekhaguere, and Lauren Fleener at the University of Iowa for their technical assistance with sample management, DNA extraction, and genotyping. We thank Sara Copeland at the Health Resources Services Administration for her guidance on this project.
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Alul, F., Shchelochkov, O., Berberich, S. et al. Genetic associations with neonatal thyroid-stimulating hormone levels. Pediatr Res 73, 484–491 (2013). https://doi.org/10.1038/pr.2013.18
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DOI: https://doi.org/10.1038/pr.2013.18
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