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

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.

doi:10.1038/s41467-018-06356-1

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

Détails

Télécharger: 30367059_BIB_ED0E30FBA866.pdf (1849.08 [Ko])
Etat: Public
Version: de l'auteur⸱e
Licence: CC BY 4.0

ID Serval

serval:BIB_ED0E30FBA866

Type

Article: article d'un périodique ou d'un magazine.

Collection

Publications

Institution

UNIL/CHUV

Titre

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

Périodique

Nature communications

Auteur⸱e⸱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.

Collaborateur⸱rice⸱s

Lifelines Cohort Study

Contributeur⸱rice⸱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

Statut éditorial

Publié

Date de publication

26/10/2018

Peer-reviewed

Oui

Volume

Numéro

Pages

4455

Langue

anglais

Notes

Publication types: Journal Article ; Meta-Analysis
Publication Status: epublish

Résumé

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.

Mots-clé

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

URN

urn:nbn:ch:serval-BIB_ED0E30FBA8669

OAI-PMH

oai:serval.unil.ch:BIB_ED0E30FBA866

DOI

10.1038/s41467-018-06356-1

Pubmed

30367059

Web of science

000448414100005

Open Access

Oui