Genetic associations with neonatal thyroid-stimulating hormone levels

Farah Y Alul; Oleg A Shchelochkov; Stanton L Berberich; Jeffrey C Murray; Kelli K Ryckman

doi:10.1038/pr.2013.18

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Genetic associations with neonatal thyroid-stimulating hormone levels

Journal article

Open access

Peer reviewed

Genetic associations with neonatal thyroid-stimulating hormone levels

Farah Y Alul, Oleg A Shchelochkov, Stanton L Berberich, Jeffrey C Murray and Kelli K Ryckman

Pediatric research, Vol.73(4 Pt 1), pp.484-491

04/2013

DOI: 10.1038/pr.2013.18

PMCID: PMC3775497

PMID: 23344678

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Abstract

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. 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. 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). 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.

Haplotypes

Humans

Male

Neonatal Screening

Intensive Care Units, Neonatal

Female

Infant, Newborn

Thyrotropin - blood

Genetic Predisposition to Disease

Genetic Association Studies

Gene Frequency

Risk Factors

Thyroid Diseases - blood

3',5'-Cyclic-AMP Phosphodiesterases - genetics

Biomarkers - blood

Chromosomes, Human, Pair 9

Chi-Square Distribution

Forkhead Transcription Factors - genetics

Gestational Age

Iowa

Phenotype

Analysis of Variance

Infant, Premature

Thyroid Diseases - genetics

Polymorphism, Single Nucleotide

Details

Title: Subtitle: Genetic associations with neonatal thyroid-stimulating hormone levels
Creators: Farah Y Alul - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Oleg A Shchelochkov
Stanton L Berberich
Jeffrey C Murray
Kelli K Ryckman
Resource Type: Journal article
Publication Details: Pediatric research, Vol.73(4 Pt 1), pp.484-491
DOI: 10.1038/pr.2013.18
PMID: 23344678
PMCID: PMC3775497
NLM abbreviation: Pediatr Res
ISSN: 1530-0447
eISSN: 1530-0447
Publisher: United States
Grant note: P30 ES005605 / NIEHS NIH HHS R01 HD052953 / NICHD NIH HHS R01 HD-52953 / NICHD NIH HHS R01 HD-65786 / NICHD NIH HHS R00 HD065786 / NICHD NIH HHS K99 HD065786 / NICHD NIH HHS R01 HD057192 / NICHD NIH HHS R01 HD-57192 / NICHD NIH HHS
Language: English
Date published: 04/2013
Academic Unit: Anatomy and Cell Biology; International Programs; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Nursing; Public Policy Center (Archive); Dental Research
Record Identifier: 9983996067502771

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