Pulse lineResearch With Heart Logo

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

TitleGenome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.
Publication TypeJournal Article
Year of Publication2018
AuthorsTeumer A, Chaker L, Groeneweg S, et al.
Secondary AuthorsMedici M
Corporate AuthorsLifeLines Cohort Study
JournalNat Commun
Volume9
Issue1
Pagination4455
Date Published2018 10 26
ISSN2041-1723
Keywords2-Aminoadipate Transaminase, Animals, Biological Transport, Chlorocebus aethiops, COS Cells, European Continental Ancestry Group, Gene Expression Regulation, Genome-Wide Association Study, Humans, Hyperthyroidism, Hypothyroidism, Polymorphism, Single Nucleotide, Risk Factors, Sodium-Phosphate Cotransporter Proteins, Type I, Thyroid Gland, Thyroid Hormones, Thyrotropin
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.

DOI10.1038/s41467-018-06356-1
Alternate JournalNat Commun
PubMed ID30367059
PubMed Central IDPMC6203810
Grant ListBB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
MR/K026992/1 / / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States