Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation
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Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. / Teumer, Alexander; Chaker, Layal; Groeneweg, Stefan; Li, Yong; Di Munno, Celia; Barbieri, Caterina; Ahluwalia, Tarunveer S; Astrup, Arne; Linneberg, Allan; Pedersen, Oluf Borbye; Sørensen, Thorkild I.A.; ThyroidOmics Consortium.
In: Nature Communications, Vol. 9, 4455, 2018.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation
AU - Teumer, Alexander
AU - Chaker, Layal
AU - Groeneweg, Stefan
AU - Li, Yong
AU - Di Munno, Celia
AU - Barbieri, Caterina
AU - Ahluwalia, Tarunveer S
AU - Astrup, Arne
AU - Linneberg, Allan
AU - Pedersen, Oluf Borbye
AU - Sørensen, Thorkild I.A.
AU - ThyroidOmics Consortium
N1 - CURIS 2018 NEXS 364
PY - 2018
Y1 - 2018
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 associatedwith 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 associatedwith 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.
KW - Faculty of Science
KW - Thyroid dysfunction
KW - Thyroid hormone regulation
KW - Genome-wide analysis
KW - Genetic variants
KW - Thyroid hormone transporter (SLC17A4)
KW - Metabolyzing hormone (AADAT)
U2 - 10.1038/s41467-018-06356-1
DO - 10.1038/s41467-018-06356-1
M3 - Journal article
C2 - 30367059
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 4455
ER -
ID: 204189806