Genetic associations with neonatal thyroid-stimulating hormone levels.
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).


CONCLUSIONS
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.
Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
Farah Y
FY
Alul
Oleg A
OA
Shchelochkov
Stanton L
SL
Berberich
Jeffrey C
JC
Murray
Kelli K
KK
Ryckman
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002899:Chromosomes, Human, Pair 9; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal; D007484:Iowa; D008297:Male; D015997:Neonatal Screening; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013959:Thyroid Diseases / Q000097:blood* / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood*
D015415:Biomarkers; C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; D013972:Thyrotropin; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C468781:PDE8B protein, human