TY - JOUR
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 - 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 - Linneberg, Allan
AU - Sørensen, Thorkild I A
AU - Thuesen, Betina
AU - LifeLines Cohort study
PY - 2018/10/26
Y1 - 2018/10/26
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.
U2 - 10.1038/s41467-018-06356-1
DO - 10.1038/s41467-018-06356-1
M3 - Journal article
C2 - 30367059
SN - 2041-1722
VL - 9
SP - 4455
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -