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.