The Genetic Basis of Thyroid Function: Novel Findings and New Approaches
Open accessAbstract
Context: 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. Evidence Acquisition: 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. Evidence Synthesis: 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. Conclusions: 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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There are more than 50 known genes whose variations each have a small influence (e.g., 1%-3%) on blood thyroid hormone levels.
“there are more than 50 known genes whose variations each have a small influence (e.g., 1% -3%) on blood thyroid hormone levels, 54”
From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [54]
The introduction (p. 1) says multiple common variants have small effects on TSH and thyroid hormone levels. Genetic Determinants of Thyroid Function (p. 2) reports 42 TSH-associated and 21 FT4-associated loci, but does not establish that these represent more than 50 distinct genes affecting blood thyroid hormone levels. The paper also does not give a 1%–3% effect for each variant. (LLM, conf=0.87)
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“%) on blood thyroid hormone levels, 54 and this probably reflects a similarly complex situation for tissue thyroid hormone regulation.”
BackgroundA Deeper Understanding of the Causal Relationships Between Thyroid Function and Atrial Fibrillation
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Self-citation
- Authors
- Kuś, A., Chaker, L., Teumer, A., Peeters, R. P., & Medici, M.
- Affiliations
- Medical University of Warsaw (PL)
- Erasmus MC (NL)
- Universitätsmedizin Greifswald (DE)
- Corresponding author
- Medici, Marco
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2020-04-09
- Volume
- 105
- Issue
- 6
- Pages
- 1707-1721
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W3015657991
- Cited by
- 44
- References
- 119
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 5 · 2022: 5 · 2021: 14 · 2020: 2
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- green
- pure.eur.nl
- Licence
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Exchange in Endocrinology Expertise
- European Union of Medical Specialists
- Section and Board of Endocrinology
- American Thyroid Association
- European Thyroid Association
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- thyroid function, genetic variants, thyroid-stimulating hormone, free thyroxine, hypothalamic-pituitary-thyroid axis, thyroid hormone regulation, Mendelian randomization, genome-wide association study
- MeSH terms
- Humans, Genetic Linkage, Prognosis, Thyroid Diseases, Thyroid Gland, Thyroid Hormones, Biomarkers, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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