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

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http://hdl.handle.net/10138/285182

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LifeLines Cohort Study 2018 , ' Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation ' , Nature Communications , vol. 9 , 4455 . https://doi.org/10.1038/s41467-018-06356-1

Title: Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation
Author: LifeLines Cohort Study
Date: 2018-10-26
Language: eng
Number of pages: 14
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/285182
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.
Subject: MONOCARBOXYLATE TRANSPORTER-8
SUBCLINICAL HYPOTHYROIDISM
REFERENCE RANGE
ASSOCIATION
RISK
IDENTIFICATION
HERITABILITY
METAANALYSIS
EFFICIENT
VARIANTS
3111 Biomedicine
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