TY - JOUR
T1 - A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents
AU - Nielsen, Tenna Ruest Haarmark
AU - Appel, Emil Vincent Rosenbaum
AU - Svendstrup, Mathilde
AU - Ohrt, Johanne Dam
AU - Dahl, Maria
AU - Fonvig, Cilius Esmann
AU - Hollensted, Mette
AU - Have, Christian Theil
AU - Kadarmideen, Haja N
AU - Pedersen, Oluf
AU - Hansen, Torben
AU - Holm, Jens-Christian
AU - Grarup, Niels
PY - 2017/3
Y1 - 2017/3
N2 - Background Hypothyroidism is associated with obesity, and thyroid hormones are involved in the regulation of body composition, including fat mass. Genome-wide association studies (GWAS) in adults have identified 19 and 6 loci associated with plasma concentrations of thyroid stimulating hormone (TSH) and free thyroxine (fT4), respectively. Objective This study aimed to identify and characterize genetic variants associated with circulating TSH and fT4 in Danish children and adolescents and to examine whether these variants associate with obesity. Methods Genome-wide association analyses of imputed genotype data with fasting plasma concentrations of TSH and fT4 from a population-based sample of Danish children, adolescents, and young adults, and a group of children, adolescents, and young adults with overweight and obesity were performed (N = 1,764, mean age = 12.0 years [range 2.5-24.7]). Replication was performed in additional comparable samples (N = 2,097, mean age = 11.8 years [1.2-22.8]). Meta-analyses, using linear additive fixed-effect models, were performed on the results of the discovery and replication analyses. Results No novel loci associated with TSH or fT4 were identified. Four loci previously associated with TSH in adults were confirmed in this study population (PDE10A (rs2983511: β = 0.112SD, p = 4.8 10-16), FOXE1 (rs7847663: β = 0.223SD, p = 1.5 10-20), NR3C2 (rs9968300: β = 0.194SD), p = 2.4 10-11), VEGFA (rs2396083: β = 0.088SD, p = 2.2 10-10)). Effect sizes of variants known to associate with TSH or fT4 in adults showed a similar direction of effect in our cohort of children and adolescents, 11 of which were associated with TSH or fT4 in our study (p<0.0002). None of the TSH or fT4 associated SNPs were associated with obesity in our cohort, indicating no pleiotropic effects of these variants on obesity. Conclusion In a group of Danish children and adolescents, four loci previously associated with plasma TSH concentrations in adults, were associated with plasma TSH concentrations in children, suggesting comparable genetic determinants of thyroid function in adults and children.
AB - Background Hypothyroidism is associated with obesity, and thyroid hormones are involved in the regulation of body composition, including fat mass. Genome-wide association studies (GWAS) in adults have identified 19 and 6 loci associated with plasma concentrations of thyroid stimulating hormone (TSH) and free thyroxine (fT4), respectively. Objective This study aimed to identify and characterize genetic variants associated with circulating TSH and fT4 in Danish children and adolescents and to examine whether these variants associate with obesity. Methods Genome-wide association analyses of imputed genotype data with fasting plasma concentrations of TSH and fT4 from a population-based sample of Danish children, adolescents, and young adults, and a group of children, adolescents, and young adults with overweight and obesity were performed (N = 1,764, mean age = 12.0 years [range 2.5-24.7]). Replication was performed in additional comparable samples (N = 2,097, mean age = 11.8 years [1.2-22.8]). Meta-analyses, using linear additive fixed-effect models, were performed on the results of the discovery and replication analyses. Results No novel loci associated with TSH or fT4 were identified. Four loci previously associated with TSH in adults were confirmed in this study population (PDE10A (rs2983511: β = 0.112SD, p = 4.8 10-16), FOXE1 (rs7847663: β = 0.223SD, p = 1.5 10-20), NR3C2 (rs9968300: β = 0.194SD), p = 2.4 10-11), VEGFA (rs2396083: β = 0.088SD, p = 2.2 10-10)). Effect sizes of variants known to associate with TSH or fT4 in adults showed a similar direction of effect in our cohort of children and adolescents, 11 of which were associated with TSH or fT4 in our study (p<0.0002). None of the TSH or fT4 associated SNPs were associated with obesity in our cohort, indicating no pleiotropic effects of these variants on obesity. Conclusion In a group of Danish children and adolescents, four loci previously associated with plasma TSH concentrations in adults, were associated with plasma TSH concentrations in children, suggesting comparable genetic determinants of thyroid function in adults and children.
KW - Adolescent
KW - Adult
KW - Age Factors
KW - Body Mass Index
KW - Child
KW - Child, Preschool
KW - Denmark
KW - Female
KW - Genetic Loci
KW - Genetic Markers
KW - Genetic Predisposition to Disease
KW - Humans
KW - Male
KW - Pediatric Obesity
KW - Polymorphism, Single Nucleotide
KW - Thyrotropin
KW - Thyroxine
KW - Young Adult
KW - Journal Article
U2 - 10.1371/journal.pone.0174204
DO - 10.1371/journal.pone.0174204
M3 - Journal article
C2 - 28333968
SN - 1932-6203
VL - 12
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 3
M1 - e0174204
ER -
