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| PMID |
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|
| TITLE |
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| Genetic determinants of thyroid function in children. |
|
| ABSTRACT |
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| OBJECTIVE |
NlmCategory: OBJECTIVE |
| Genome-wide association studies in adults have identified 42 loci associated with thyroid stimulating hormone (TSH) and 21 loci associated with free thyroxine (FT4) concentrations. While biologically plausible, age-dependent effects have not been assessed. We aimed to study the association of previously identified genetic determinants of TSH and FT4 with TSH and FT4 concentrations in newborns and (pre)school children. |
| METHODS |
NlmCategory: METHODS |
| Genome-wide association studies in adults have identified 42 loci associated with thyroid stimulating hormone (TSH) and 21 loci associated with free thyroxine (FT4) concentrations. While biologically plausible, age-dependent effects have not been assessed. We aimed to study the association of previously identified genetic determinants of TSH and FT4 with TSH and FT4 concentrations in newborns and (pre)school children. We selected participants from three population-based prospective cohorts with data on genetic variants and thyroid function: Generation R (N = 2169 children, mean age 6 years; N = 2388 neonates, the Netherlands), the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3382, age 7.5 years, United Kingdom), and the Brisbane Longitudinal Twin Study (BLTS; N = 1680, age 12.1 years, Australia). The association of single nucleotide polymorphisms (SNPs) with TSH and FT4 concentrations was studied with multivariable linear regression models. Weighted polygenic risk scores (PRSs) were defined to combine SNP effects. |
| RESULTS |
NlmCategory: RESULTS |
| Genome-wide association studies in adults have identified 42 loci associated with thyroid stimulating hormone (TSH) and 21 loci associated with free thyroxine (FT4) concentrations. While biologically plausible, age-dependent effects have not been assessed. We aimed to study the association of previously identified genetic determinants of TSH and FT4 with TSH and FT4 concentrations in newborns and (pre)school children. We selected participants from three population-based prospective cohorts with data on genetic variants and thyroid function: Generation R (N = 2169 children, mean age 6 years; N = 2388 neonates, the Netherlands), the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3382, age 7.5 years, United Kingdom), and the Brisbane Longitudinal Twin Study (BLTS; N = 1680, age 12.1 years, Australia). The association of single nucleotide polymorphisms (SNPs) with TSH and FT4 concentrations was studied with multivariable linear regression models. Weighted polygenic risk scores (PRSs) were defined to combine SNP effects. In childhood, 30/60 SNPs were associated with TSH and 11/31 SNPs with FT4 after multiple testing correction. The effect sizes for AADAT, GLIS3, TM4SF4, and VEGFA were notably larger than in adults. The TSH PRS explained 5.3%-8.4% of the variability in TSH concentrations; the FT4 PRS explained 1.5%-4.2% of the variability in FT4 concentrations. Five TSH SNPs and no FT4 SNPs were associated with thyroid function in neonates. |
| CONCLUSIONS |
NlmCategory: CONCLUSIONS |
| Genome-wide association studies in adults have identified 42 loci associated with thyroid stimulating hormone (TSH) and 21 loci associated with free thyroxine (FT4) concentrations. While biologically plausible, age-dependent effects have not been assessed. We aimed to study the association of previously identified genetic determinants of TSH and FT4 with TSH and FT4 concentrations in newborns and (pre)school children. We selected participants from three population-based prospective cohorts with data on genetic variants and thyroid function: Generation R (N = 2169 children, mean age 6 years; N = 2388 neonates, the Netherlands), the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3382, age 7.5 years, United Kingdom), and the Brisbane Longitudinal Twin Study (BLTS; N = 1680, age 12.1 years, Australia). The association of single nucleotide polymorphisms (SNPs) with TSH and FT4 concentrations was studied with multivariable linear regression models. Weighted polygenic risk scores (PRSs) were defined to combine SNP effects. In childhood, 30/60 SNPs were associated with TSH and 11/31 SNPs with FT4 after multiple testing correction. The effect sizes for AADAT, GLIS3, TM4SF4, and VEGFA were notably larger than in adults. The TSH PRS explained 5.3%-8.4% of the variability in TSH concentrations; the FT4 PRS explained 1.5%-4.2% of the variability in FT4 concentrations. Five TSH SNPs and no FT4 SNPs were associated with thyroid function in neonates. The effects of many known thyroid function SNPs are already apparent in childhood and some might be notably larger in children as compared to adults. These findings provide new knowledge about genetic regulation of thyroid function in early life. |
| © The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2023/02/10 |
| revised |
2023/04/20 |
| accepted |
2023/06/06 |
| medline |
2023/08/07 06:42 |
| pubmed |
2023/08/02 13:09 |
| entrez |
2023/08/02 07:42 |
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| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Mulder TA |
|
Mulder |
Tessa A |
TA |
|
Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, CA 3000, The Netherlands. |
| Campbell PJ |
|
Campbell |
Purdey J |
PJ |
|
Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia. |
| Taylor PN |
|
Taylor |
Peter N |
PN |
|
Thyroid Research Group, Cardiff University School of Medicine, Cardiff, CF14 4YS, United Kingdom. |
| Peeters RP |
|
Peeters |
Robin P |
RP |
|
Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, CA 3000, The Netherlands. |
| Wilson SG |
|
Wilson |
Scott G |
SG |
|
Department of Twin Research & Genetic Epidemiology, King's College London, London, WC2R 2LS, United Kingdom. |
| Medici M |
|
Medici |
Marco |
M |
|
Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, CA 3000, The Netherlands. |
| Dayan C |
|
Dayan |
Colin |
C |
|
Center for Endocrine and Diabetes Science, Cardiff University School of Medicine, Cardiff, CF14 4YS, United Kingdom. |
| Jaddoe VVW |
|
Jaddoe |
Vincent V W |
VVW |
|
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands. |
| Walsh JP |
|
Walsh |
John P |
JP |
|
Medical School, The University of Western Australia, Crawley, WA 6009, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia. |
| Tiemeier H |
|
Tiemeier |
Henning |
H |
|
Department of Social and Behavioral Science, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States. |
| Korevaar TIM |
|
Korevaar |
Tim I M |
TIM |
|
Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, CA 3000, The Netherlands. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: 189 |
| ISSUE: 2 |
| TITLE: European journal of endocrinology |
| ISOABBREVIATION: Eur J Endocrinol |
| YEAR: 2023 |
| MONTH: Aug |
| DAY: 02 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1479-683X |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Eur J Endocrinol |
| COUNTRY: England |
| ISSNLINKING: 0804-4643 |
| NLMUNIQUEID: 9423848 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
|
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| GRANTS |
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| GRANTID |
AGENCY |
COUNTRY |
|
Wellcome Trust |
United Kingdom |
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| GENERAL NOTE |
|
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| KEYWORDS |
|
| KEYWORD |
| childhood |
| genetic risk score |
| genetic variants |
| thyroid function |
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| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adult |
|
| Humans |
|
| Child |
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| Infant, Newborn |
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| Child, Preschool |
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| Thyroid Gland |
physiology |
| Thyroxine |
physiology |
| Prospective Studies |
physiology |
| Longitudinal Studies |
physiology |
| Genome-Wide Association Study |
physiology |
| Thyrotropin |
physiology |
| Thyroid Function Tests |
physiology |
| Membrane Glycoproteins |
genetics |
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| SUPPLEMENTARY MESH |
|
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| GENE SYMBOLS |
|
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| CHEMICALS |
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| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| Q51BO43MG4 |
Thyroxine |
| 9002-71-5 |
Thyrotropin |
| 0 |
TM4SF4 protein, human |
| 0 |
Membrane Glycoproteins |
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| OTHER ID's |
|
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|
