Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Details

Serval ID
serval:BIB_ED0E30FBA866
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.
Journal
Nature communications
Author(s)
Teumer A., Chaker L., Groeneweg S., Li Y., Di Munno C., Barbieri C., Schultheiss U.T., Traglia M., Ahluwalia T.S., Akiyama M., Appel EVR, 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., den Hollander W., Homuth G., Hui J., Ikram M.A., Ittermann T., Jensen R.A., Jing J., Jukema J.W., Kajantie E., Kamatani Y., Kasbohm E., Kaufman J.M., Kiemeney L.A., Kloppenburg M., Kronenberg F., Kubo M., Lahti J., Lapauw B., Li S., Liewald DCM, Lim E.M., Linneberg A., Marina M., Mascalzoni D., Matsuda K., Medenwald D., Meisinger C., Meulenbelt I., De Meyer T., Meyer Zu Schwabedissen H.E., Mikolajczyk R., Moed M., Netea-Maier R.T., Nolte I.M., Okada Y., Pala M., Pattaro C., Pedersen O., Petersmann A., Porcu E., Postmus I., Pramstaller P.P., Psaty B.M., Ramos YFM, Rawal R., Redmond P., Richards J.B., Rietzschel E.R., Rivadeneira F., Roef G., Rotter J.I., Sala C.F., Schlessinger D., Selvin E., Slagboom P.E., Soranzo N., Sørensen TIA, Spector T.D., Starr J.M., Stott D.J., Taes Y., Taliun D., Tanaka T., Thuesen B., Tiller D., Toniolo D., Uitterlinden A.G., Visser W.E., Walsh J.P., Wilson S.G., Wolffenbuttel BHR, Yang Q., Zheng H.F., Cappola A., Peeters R.P., Naitza S., Völzke H., Sanna S., Köttgen A., Visser T.J., Medici M.
Working group(s)
Lifelines Cohort Study
Contributor(s)
Alizadeh B.Z., Boezen H.M., Franke L., van der Harst P., Navis G., Rots M., Snieder H., Swertz M.A., Wijmenga C.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
26/10/2018
Peer-reviewed
Oui
Volume
9
Number
1
Pages
4455
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis
Publication Status: epublish
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.
Keywords
2-Aminoadipate Transaminase/genetics, 2-Aminoadipate Transaminase/metabolism, Animals, Biological Transport, COS Cells, Cercopithecus aethiops, European Continental Ancestry Group, Gene Expression Regulation/genetics, Genome-Wide Association Study, Humans, Hyperthyroidism/genetics, Hyperthyroidism/physiopathology, Hypothyroidism/genetics, Hypothyroidism/physiopathology, Polymorphism, Single Nucleotide, Risk Factors, 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
Pubmed
Web of science
Open Access
Yes
Create date
09/11/2018 15:16
Last modification date
21/08/2019 6:34
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