Genetic determination of the hypothalamic-pituitary-thyroid axis: where do we stand?

Area of Science:

• Endocrinology
• Genetics
• Molecular Biology

Background:

• Thyroid dysfunction (hypo- and hyperthyroidism) is linked to increased morbidity and mortality.
• Subtle thyroid function variations, including within-range changes, affect bone density, mood, metabolic syndrome, and cardiovascular health.
• Individual thyroid function setpoints exhibit significant heritability (40-60%), suggesting a strong genetic basis.

Purpose of the Study:

• To review current knowledge on the polygenic basis of thyroid (dys)function.
• To highlight newly identified candidate genes through genome-wide association studies.
• To discuss future techniques for understanding thyroid (dys)function genetics.

Main Methods:

• Review of existing literature on thyroid function genetics.
• Analysis of genome-wide association studies (GWAS) and candidate gene studies.
• Synthesis of findings on genetic variants influencing thyroid parameters.

Main Results:

• While rare mutations are known, common genetic variants (polymorphisms) influencing thyroid function are less understood.
• Recent advances have identified numerous new candidate genes through genome-wide approaches.
• These findings provide insights into the complex genetic architecture of thyroid (dys)function.

Conclusions:

• Thyroid (dys)function is polygenic, influenced by multiple genes with varying effects.
• Continued genetic research, utilizing advanced techniques, is crucial for a comprehensive understanding.
• Identifying genetic factors can lead to better prediction and management of thyroid-related conditions.