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Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation
- Source :
- Nature communications, vol. 9, no. 1, pp. 4455, Nature Communications, 9(1):4455. Nature Publishing Group, Nature Communications, 9, Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018), Nature Communications, Teumer, A, Chaker, L, Groeneweg, S, Li, Y, Di Munno, C, Barbieri, C, Ahluwalia, T S, Astrup, A, Linneberg, A, Pedersen, O B, Sørensen, T I A & ThyroidOmics Consortium 2018, ' Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation ', Nature Communications, vol. 9, 4455 . https://doi.org/10.1038/s41467-018-06356-1, Nat. Commun. 9:4455 (2018), Lifelines Cohort Study 2018, ' Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation ', Nature Communications, vol. 9, no. 1, 4455 . https://doi.org/10.1038/s41467-018-06356-1, Nat Commun, Nature Communications, 9:4455. Nature Publishing Group, Teumer, A, Chaker, L, Groeneweg, S, Li, Y, Di Munno, C, Barbieri, C, Schultheiss, U T, Traglia, M, Ahluwalia, T S, Akiyama, M, Appel, E V R, Arking, D E, Arnold, A, Astrup, A, Beekman, M, Beilby, J P, Bekaert, S, Boerwinkle, E, Brown, S J, De Buyzere, M, Campbell, P J, Ceresini, G, Cerqueira, C, Cucca, F, Deary, I J, Deelen, J, Eckardt, K-U, Ekici, A B, Eriksson, J G, Ferrrucci, L, Fiers, T, Fiorillo, E, Ford, I, Fox, C S, Fuchsberger, C, Galesloot, T E, Gieger, C, Gögele, M, De Grandi, A, Grarup, N, Greiser, K H, Haljas, K, Hansen, T, Harris, S E, van Heemst, D, den Heijer, M, Hicks, A A, Liewald, D C M, Redmond, P, Starr, J M, Stott, D J, Taes, Y E, Taliun, D, Toshiko, T, Thuesen, B, Tiller, D, Toniolo, D, Uitterlinden, A G, Visser, W E, Walsh, J P, Wilson, S G, Wolffenbuttel, B H R, Yang, Q, Zheng, H-F, Cappola, A R, Peeters, R P, Naitza, S, Völzke, H, Sanna, S, Köttgen, A, Visser, T J & Medici, M 2018, ' Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation ', Nature Communications, vol. 9, no. 1, pp. 1-14 . https://doi.org/10.1038/s41467-018-06356-1, NATURE COMMUNICATIONS
- Publication Year :
- 2018
-
Abstract
- Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves’ disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.<br />Thyroid dysfunction is a common public health problem and associated with cardiovascular co-morbidities. Here, the authors carry out genome-wide meta-analysis for thyroid hormone (TH) levels, hyper- and hypothyroidism and identify SLC17A4 as a TH transporter and AADAT as a TH metabolizing enzyme.
- Subjects :
- 0301 basic medicine
Genetic variants
endocrine system diseases
Vascular damage Radboud Institute for Health Sciences [Radboudumc 16]
Thyroid Gland
Thyrotropin
Metabolyzing hormone (AADAT)
General Physics and Astronomy
EFFICIENT
Genome-wide association study
Thyroid hormone transporter (SLC17A4)
Disease
VARIANTS
Bioinformatics
Hyperthyroidism
DISEASE
0302 clinical medicine
SUBCLINICAL HYPOTHYROIDISM
Risk Factors
Genome-wide analysis
Chlorocebus aethiops
Faculty of Science
Medicine
lcsh:Science
POPULATION
RISK
education.field_of_study
Multidisciplinary
HERITABILITY
Thyroid disease
Thyroid
Thyroid dysfunction
ASSOCIATION
3. Good health
medicine.anatomical_structure
Urological cancers Radboud Institute for Health Sciences [Radboudumc 15]
COS Cells
Thyroid function
Sodium-Phosphate Cotransporter Proteins, Type I
Thyroid Hormones
endocrine system
PARTICIPANT DATA-ANALYSIS
Science
Population
030209 endocrinology & metabolism
Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9]
Polymorphism, Single Nucleotide
White People
Article
General Biochemistry, Genetics and Molecular Biology
MONOCARBOXYLATE TRANSPORTER-8
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
Hypothyroidism
Animals
Humans
ddc:610
education
METAANALYSIS
Genetic association
2-Aminoadipate Transaminase
IDENTIFICATION
business.industry
Biology and Life Sciences
Biological Transport
General Chemistry
REFERENCE RANGE
medicine.disease
R1
2-Aminoadipate Transaminase/genetics
2-Aminoadipate Transaminase/metabolism
Cercopithecus aethiops
European Continental Ancestry Group
Gene Expression Regulation/genetics
Genome-Wide Association Study
Hyperthyroidism/genetics
Hyperthyroidism/physiopathology
Hypothyroidism/genetics
Hypothyroidism/physiopathology
Sodium-Phosphate Cotransporter Proteins, Type I/genetics
Sodium-Phosphate Cotransporter Proteins, Type I/metabolism
Thyroid Gland/metabolism
Thyroid Gland/physiopathology
Thyroid Hormones/genetics
Thyroid Hormones/metabolism
Thyrotropin/metabolism
030104 developmental biology
Gene Expression Regulation
ATRIAL-FIBRILLATION
lcsh:Q
3111 Biomedicine
business
Thyroid hormone regulation
Hormone
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....121e7b6174ad0cbd3fcf7d39e1f917e5
- Full Text :
- https://doi.org/10.1038/s41467-018-06356-1