The Genetic Basis of Thyroid Function: Novel Findings and New Approaches

Genetic factors are major determinants of thyroid function. Over the last two decades, multiple genetic variants have been associated with variations in normal range thyroid function tests. Most recently, a large-scale genome-wide association study (GWAS) doubled the number of known variants associa...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism Vol. 105; no. 6; pp. 1707 - 1721
Main Authors: Kuś, Aleksander, Chaker, Layal, Teumer, Alexander, Peeters, Robin P, Medici, Marco
Format: Journal Article
Language:English
Published: United States Oxford University Press 01.06.2020
Subjects:
Biomarkers - analysis
Genetic diversity
Genetic factors
Genetic Linkage
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genotype
Health aspects
Humans
Hypothalamic-pituitary-thyroid axis
Hypothalamus
Identification and classification
Methods
Observations
Pituitary
Polymorphism, Single Nucleotide
Prognosis
Thyroid diseases
Thyroid Diseases - blood
Thyroid Diseases - genetics
Thyroid Diseases - physiopathology
Thyroid gland
Thyroid Gland - physiology
Thyroid gland function tests
Thyroid Hormones - blood
Thyroid-stimulating hormone
Thyrotropin
Thyroxine
Netherlands
TSH
genetics
thyroid
single nucleotide polymorphism
FT4
genome-wide association study
ISSN:0021-972X, 1945-7197, 1945-7197
Online Access:Get full text
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Summary:Genetic factors are major determinants of thyroid function. Over the last two decades, multiple genetic variants have been associated with variations in normal range thyroid function tests. Most recently, a large-scale genome-wide association study (GWAS) doubled the number of known variants associated with normal range thyrotropin (TSH) and free thyroxine (FT4) levels. This review summarizes the results of genetic association studies on normal range thyroid function and explores how these genetic variants can be used in future studies to improve our understanding of thyroid hormone regulation and disease. Serum TSH and FT4 levels are determined by multiple genetic variants on virtually all levels of the hypothalamus-pituitary-thyroid (HPT) axis. Functional follow-up studies on top of GWAS hits has the potential to discover new key players in thyroid hormone regulation, as exemplified by the identification of the thyroid hormone transporter SLC17A4 and the metabolizing enzyme AADAT. Translational studies may use these genetic variants to investigate causal associations between thyroid function and various outcomes in Mendelian Randomization (MR) studies, to identify individuals with an increased risk of thyroid dysfunction, and to predict the individual HPT axis setpoint. Recent genetic studies have greatly improved our understanding of the genetic basis of thyroid function, and have revealed novel pathways involved in its regulation. In addition, these findings have paved the way for various lines of research that can improve our understanding of thyroid hormone regulation and thyroid diseases, as well as the potential use of these markers in future clinical practice.
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ISSN:0021-972X
1945-7197
1945-7197
DOI:10.1210/clinem/dgz225