Dataset Information

Genetic associations with neonatal thyroid-stimulating hormone levels.

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.

SUBMITTER: Alul FY

PROVIDER: S-EPMC3775497 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic associations with neonatal thyroid-stimulating hormone levels.

Alul Farah Y FY Shchelochkov Oleg A OA Berberich Stanton L SL Murray Jeffrey C JC Ryckman Kelli K KK

Pediatric research 20130123 4 Pt 1

<h4>Background</h4>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.<h4>Methods</h4>A population of Iowa neonates, term (n = 827) and preterm (n = 815), were genotyped for 45 single-nucleotide polymorphisms (SNPs). Thyroi ...[more]

PMID: 23344678

Similar Datasets

Project description:BackgroundNormal brain development is dependent on maternal, fetal and neonatal thyroid function. Measuring neonatal thyroid-stimulating hormone (TSH) 48-72 hours after birth screens for congenital hypothyroidism, allowing early treatment to avoid serious impairment. However, even within sub-clinical ranges, disrupted thyroid homeostasis during brain development has been linked to adverse neurodevelopmental outcomes, including attention-deficit/hyperactivity disorder (ADHD).ObjectivesTo estimate the association between neonatal TSH below threshold for potential congenital hypothyroidism and subsequent ADHD diagnosis using a population-based birth cohort.MethodsChildren with a diagnosis of ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa) were identified through linkage with the Norwegian Patient Registry using ICD-10 codes for hyperkinetic disorders. The study included 405 ADHD cases and 1,092 controls (born 2003-2008) with available neonatal TSH concentrations below 10 mU/L (cut-off for potential congenital hypothyroidism) measured in dried blood spots sampled 48-72 hours after birth.ResultsIn multivariable, quintile models the relationship appeared to follow a U-shaped pattern with elevated odds ratios (OR) at lower and higher TSH levels. Among children with TSH in the lowest quintile, odds of ADHD was approximately 1.5-fold higher than children in the middle quintile (OR 1.60, 95% CI 1.09, 2.34), which was driven by substantially elevated risk among girls, with no association among boys (Pinteraction = 0.02; girls OR 3.10, 95% CI 1.53, 6.30; boys OR 1.16, 95% CI 0.73, 1.84).ConclusionsADHD risk appeared to be elevated among newborns with low TSH levels (i.e. with hyperthyroid status), and this association was mainly found among girls. Because our findings are suggestive of increased risk at very low TSH concentrations, where analytical accuracy is low, future studies should employ highly sensitive assays capable of accurate quantitation at very low concentrations. Also, larger studies are needed to investigate these associations at higher neonatal TSH concentrations where data are more widely distributed.

Dataset Information

Genetic associations with neonatal thyroid-stimulating hormone levels.

Background

Methods

Results

Conclusion

Publications

Genetic associations with neonatal thyroid-stimulating hormone levels.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets