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

Lifelines Cohort Study

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Article number4455
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 01-12-2018

Fingerprint

hormones
genome
Thyroid Hormones
Genes
Thyroid Diseases
Genome
Thyroid Gland
Genome-Wide Association Study
Graves Disease
Physiology
Public health
Medical problems
Metabolism
public health
transporter
physiology
Meta-Analysis
mortality
metabolism
Public Health

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

@article{e836dc269cba432c81094373dff8a637,
title = "Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation",
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.",
author = "{Lifelines Cohort Study} and Alexander Teumer and Layal Chaker and Stefan Groeneweg and Yong Li and {Di Munno}, Celia and Caterina Barbieri and Schultheiss, {Ulla T.} and Michela Traglia and Ahluwalia, {Tarunveer S.} and Masato Akiyama and Appel, {Emil Vincent R.} and Arking, {Dan E.} and Alice Arnold and Arne Astrup and Marian Beekman and Beilby, {John P.} and Sofie Bekaert and Eric Boerwinkle and Brown, {Suzanne J.} and {De Buyzere}, Marc and Campbell, {Purdey J.} and Graziano Ceresini and Charlotte Cerqueira and Francesco Cucca and Deary, {Ian J.} and Joris Deelen and Eckardt, {Kai Uwe} and Ekici, {Arif B.} and Eriksson, {Johan G.} and Luigi Ferrrucci and Tom Fiers and Edoardo Fiorillo and Ian Ford and Fox, {Caroline S.} and Christian Fuchsberger and Galesloot, {Tessel E.} and Christian Gieger and Martin G{\"o}gele and {De Grandi}, Alessandro and Niels Grarup and Greiser, {Karin Halina} and Kadri Haljas and Torben Hansen and Harris, {Sarah E.} and {van Heemst}, Diana and {den Heijer}, Martin and Hicks, {Andrew A.} and {den Hollander}, Wouter and Georg Homuth and Jennie Hui",
year = "2018",
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language = "English",
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Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. / Lifelines Cohort Study.

In: Nature Communications, Vol. 9, No. 1, 4455, 01.12.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation

AU - Lifelines Cohort Study

AU - Teumer, Alexander

AU - Chaker, Layal

AU - Groeneweg, Stefan

AU - Li, Yong

AU - Di Munno, Celia

AU - Barbieri, Caterina

AU - Schultheiss, Ulla T.

AU - Traglia, Michela

AU - Ahluwalia, Tarunveer S.

AU - Akiyama, Masato

AU - Appel, Emil Vincent R.

AU - Arking, Dan E.

AU - Arnold, Alice

AU - Astrup, Arne

AU - Beekman, Marian

AU - Beilby, John P.

AU - Bekaert, Sofie

AU - Boerwinkle, Eric

AU - Brown, Suzanne J.

AU - De Buyzere, Marc

AU - Campbell, Purdey J.

AU - Ceresini, Graziano

AU - Cerqueira, Charlotte

AU - Cucca, Francesco

AU - Deary, Ian J.

AU - Deelen, Joris

AU - Eckardt, Kai Uwe

AU - Ekici, Arif B.

AU - Eriksson, Johan G.

AU - Ferrrucci, Luigi

AU - Fiers, Tom

AU - Fiorillo, Edoardo

AU - Ford, Ian

AU - Fox, Caroline S.

AU - Fuchsberger, Christian

AU - Galesloot, Tessel E.

AU - Gieger, Christian

AU - Gögele, Martin

AU - De Grandi, Alessandro

AU - Grarup, Niels

AU - Greiser, Karin Halina

AU - Haljas, Kadri

AU - Hansen, Torben

AU - Harris, Sarah E.

AU - van Heemst, Diana

AU - den Heijer, Martin

AU - Hicks, Andrew A.

AU - den Hollander, Wouter

AU - Homuth, Georg

AU - Hui, Jennie

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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