Thyroid Disease
The thyroid gland, a butterfly-shaped organ located in the neck, plays a crucial role in regulating the body’s metabolism through the production of thyroid hormones, primarily thyroxine (T4) and triiodothyronine (T3). These hormones influence nearly every cell in the body, affecting energy levels, heart rate, body temperature, and growth. Thyroid disease refers to a range of conditions that impair the thyroid gland’s ability to produce the correct amount of these hormones. This can lead to either an overactive thyroid (hyperthyroidism) or an underactive thyroid (hypothyroidism).
Genetic factors are known to significantly influence thyroid function and susceptibility to various thyroid disorders. Studies have shown a major genetic influence on the regulation of the pituitary-thyroid axis and variation in thyroid hormone levels[1]. Genetic heterogeneity and gene interactions are implicated in the susceptibility to familial Graves’ and Hashimoto’s diseases, which are common autoimmune thyroid conditions [2]. Familial studies of autoimmune thyroiditis have also highlighted the genetic predisposition to these conditions [3].
Thyroid diseases are among the most common endocrine disorders worldwide, affecting millions of people and impacting quality of life due to a wide array of symptoms that can mimic other conditions. Early diagnosis and appropriate treatment are critical to manage symptoms, prevent complications, and maintain overall health. Clinical relevance extends to conditions like goiter, thyroid nodules, and thyroid cancer, alongside the more prevalent hypo- and hyperthyroidism. Understanding the genetic underpinnings of thyroid disease is socially important as it can lead to improved risk assessment, more targeted screening programs, and the development of personalized treatment strategies. Research, including genome-wide association studies (GWAS), continues to identify specific genetic variants that contribute to the risk and progression of these conditions, offering insights into disease mechanisms and potential therapeutic targets.
Limitations
Section titled “Limitations”Understanding the genetic basis of thyroid disease, like many complex traits, is subject to several inherent limitations that influence the interpretation and generalizability of research findings. These limitations arise from the study designs, statistical power, methods of phenotypic assessment, and the complex interplay of genetic and environmental factors.
Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”Genetic association studies for thyroid disease often face challenges related to study design and statistical power. The initial discovery phases of genome-wide association studies (GWAS) may have a relatively modest sample size, which can limit their power to detect associations, especially for variants with smaller effect sizes[4]. For instance, some studies calculate an initial GWAS might have only approximately 50% power to detect an odds ratio of 2.0 with a significance level of 0.05 [4]. To mitigate the risk of false positives, a staged study design, including replication and fine-mapping stages, is crucial to confirm associations and reduce spurious findings [4]. However, incomplete coverage of common genetic variation across the genome, and particularly poor coverage of rare variants, can mean that many susceptibility effects remain undiscovered and significant genes might be missed [5].
Furthermore, the statistical approaches used in GWAS must account for multiple comparisons, which can be challenging. While conservative corrections can mask associations of moderate effect size, a rigorous replication strategy is essential to validate findings[4]. Even with robust statistical methods, the identified genetic variants individually or in combination have not yet been shown to provide clinically useful prediction for many diseases, indicating that much of the genetic heritability remains unexplained [5]. This “missing heritability” suggests that current methods may not fully capture the complex genetic architecture, including interactions between genes or the influence of rare variants.
Phenotypic Definition and Population Generalizability
Section titled “Phenotypic Definition and Population Generalizability”The definition and measurement of thyroid disease can introduce variability and potential biases into genetic studies. Reliance on self-reported thyroid disease status, which may include autoimmune thyroiditis, thyroid cancer, or a history of partial or total thyrectomy, and information on hormone-replacement therapy, can be less precise than objective clinical diagnoses[6]. While measurements of serum TSH levels provide a quantitative phenotype, the broader categorization of “thyroid disease” based on self-report could lead to heterogeneity within case groups, potentially diluting genetic signals.
Additionally, the generalizability of findings across diverse populations is a significant concern. Studies conducted in specific populations, such as those from isolated founder populations, may reveal unique genetic insights but their applicability to broader, more genetically diverse populations can be limited [7]. While population structure correction methods aim to minimize confounding effects, strong geographical differentiation in certain genomic regions necessitates cautious interpretation of associations in those areas, highlighting the need for replication in varied ancestral groups [5]. The genetic landscape of thyroid disease may vary significantly between ethnic groups, meaning that findings from one population may not directly translate to another.
Unaccounted Environmental Factors and Remaining Knowledge Gaps
Section titled “Unaccounted Environmental Factors and Remaining Knowledge Gaps”The complexity of thyroid disease etiology extends beyond genetics to include environmental factors and gene-environment interactions, which are often not fully captured or accounted for in current studies. While genetic associations are identified, the complete picture of how genes interact with lifestyle, diet, exposure to toxins, or other environmental triggers remains largely unexplored within the provided context. The “missing heritability” observed in complex diseases suggests that many susceptibility effects are yet to be uncovered, implying that either unmeasured genetic factors (e.g., rare variants, structural variants, epigenetic modifications) or uncharacterized environmental influences and their interactions play substantial roles[5].
Current research, while identifying significant genetic loci, acknowledges that failure to detect a prominent association signal for a specific gene does not conclusively exclude its involvement in thyroid disease[5]. This highlights the ongoing need for more comprehensive studies that integrate multi-omics data, detailed environmental exposures, and longitudinal phenotypic assessments to fully elucidate the complex genetic and environmental architecture underlying thyroid disease. The identified genetic variants, while important, represent only a part of the overall risk, and substantial knowledge gaps persist regarding the full spectrum of genetic and non-genetic contributors.
Variants
Section titled “Variants”Genetic variations play a crucial role in determining an individual’s susceptibility to thyroid diseases, ranging from autoimmune conditions to thyroid cancer. These variants often affect genes involved in thyroid development, hormone synthesis, or immune regulation. Understanding these genetic influences helps to elucidate the complex mechanisms underlying thyroid dysfunction and disease.
Variants near the FOXE1 gene on chromosome 9q22.33, such as rs965513 , are strongly associated with an increased risk of thyroid cancer. TheFOXE1 gene, also known as TTF2, is a transcription factor essential for the embryonic development and differentiation of the thyroid gland, regulating genes like TG (thyroglobulin) and TPO (thyroid peroxidase) [8]. The A-allele of rs965513 significantly increases the risk for both papillary (PTC) and follicular (FTC) thyroid cancer, with an odds ratio of 1.80 for PTC and 1.55 for FTC[8]. Homozygous carriers of this allele face a 3.1-fold greater risk, and its presence is also linked to an earlier age of diagnosis [8]. Additionally, this allele is associated with lower levels of thyroid stimulating hormone (TSH) and thyroxine (T4), and higher levels of triiodothyronine (T3), indicating its influence on overall thyroid function[8]. Other variants in this region, including rs7030241 and rs7850258 within the PTCSC2locus, are also implicated in modulating thyroid disease risk, likely by affecting the regulatory landscape of nearby genes critical for thyroid health.
Several variants contribute to the genetic predisposition for autoimmune thyroid diseases, which include Graves’ disease and Hashimoto’s thyroiditis. Polymorphisms in the Human Leukocyte Antigen (HLA) complex, such asrs9272293 in HLA-DQA1 and rs3134996 in HLA-DQB1, are particularly significant. HLA genes encode proteins on the surface of immune cells that present antigens, playing a central role in immune recognition and self-tolerance; specific HLA alleles can increase the risk of the immune system mistakenly attacking thyroid tissue. Similarly, the rs2476601 variant in PTPN22 (Protein Tyrosine Phosphatase Non-Receptor Type 22) is a well-established risk factor for various autoimmune conditions, including autoimmune thyroiditis, by affecting T-cell activation and regulating immune responses. Another key immunoregulatory gene, CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4), with variants like rs3087243 , acts as an immune checkpoint, dampening T-cell activity to prevent excessive immune responses, and its dysfunction can lead to autoimmune attacks on the thyroid gland.
Beyond these primary drivers, other genetic variants contribute to the nuanced landscape of thyroid function and disease. Variants such asrs7310615 and rs3184504 in the SH2B3gene, which encodes an adaptor protein involved in cytokine signaling and hematopoietic cell development, can influence immune cell growth and differentiation, potentially modulating autoimmune susceptibility and inflammatory responses within the thyroid. TheTPOgene, encoding thyroid peroxidase, is critical for thyroid hormone synthesis, and variants likers11675342 and rs11211645 can impact enzyme activity or protein stability, affecting hormone production and contributing to thyroid dysfunction or autoimmune reactions where TPO is a primary autoantigen. Furthermore, genes likeVAV3 (rs17020127 , rs78495697 ) and the region associated with PHTF1 and RSBN1 (rs6679677 ), which are involved in cellular signaling and regulation, may also play roles in the development, proliferation, or immune responses of thyroid cells, thereby influencing overall thyroid health and disease risk.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs965513 rs7030241 rs7850258 | PTCSC2 | thyroid carcinoma hypothyroidism goiter thyroid disease |
| rs9272293 | HLA-DQA1 | sperm acrosome membrane-associated protein 3 measurement thyroid disease hypothyroidism HPV seropositivity |
| rs6679677 | PHTF1 - RSBN1 | rheumatoid arthritis, celiac disease type 1 diabetes mellitus rheumatoid arthritis hypothyroidism keratinocyte carcinoma |
| rs3087243 | CTLA4 - ICOS | type 1 diabetes mellitus rheumatoid arthritis hypothyroidism non-melanoma skin carcinoma systemic lupus erythematosus |
| rs7310615 | SH2B3 | circulating fibrinogen levels systolic blood pressure, alcohol consumption quality systolic blood pressure, alcohol drinking mean arterial pressure, alcohol drinking mean arterial pressure, alcohol consumption quality |
| rs3184504 | ATXN2, SH2B3 | beta-2 microglobulin measurement hemoglobin measurement lung carcinoma, estrogen-receptor negative breast cancer, ovarian endometrioid carcinoma, colorectal cancer, prostate carcinoma, ovarian serous carcinoma, breast carcinoma, ovarian carcinoma, squamous cell lung carcinoma, lung adenocarcinoma platelet crit coronary artery disease |
| rs2476601 | PTPN22, AP4B1-AS1 | rheumatoid arthritis autoimmune thyroid disease, type 1 diabetes mellitus leukocyte quantity ankylosing spondylitis, psoriasis, ulcerative colitis, Crohn’s disease, sclerosing cholangitis late-onset myasthenia gravis |
| rs3134996 | HLA-DQB1 - MTCO3P1 | thyroid disease hypothyroidism |
| rs11675342 rs11211645 | TPO | hypothyroidism autoimmune thyroid disease thyroid stimulating hormone amount autoimmune disease Thyroid preparation use measurement |
| rs17020127 rs78495697 | VAV3 | thyroid stimulating hormone amount hypothyroidism thyroid disease |
Clinical Assessment and Phenotypic Diversity
Section titled “Clinical Assessment and Phenotypic Diversity”The clinical presentation of thyroid disease exhibits significant phenotypic diversity, encompassing conditions such as autoimmune thyroiditis, thyroid cancer, and states following partial or total thyrectomy[6]. Information regarding these varied conditions is frequently gathered through self-reported thyroid disease status, which offers valuable subjective insights into an individual’s health history and experiences[6].
Complementing subjective reports, objective assessment methods like ultrasound and color-Doppler sonography are employed to meticulously determine the presence, structure, size, and vascularization of thyroid nodules[6]. These diverse factors underscore the heterogeneous nature of thyroid disease presentation and its diagnostic challenges.
Causes of Thyroid Disease
Section titled “Causes of Thyroid Disease”Thyroid disease arises from a complex interplay of genetic predispositions, environmental factors, and their dynamic interactions, affecting the gland’s ability to produce or regulate hormones essential for metabolism.
Genetic Predisposition and Heredity
Section titled “Genetic Predisposition and Heredity”Familial forms of thyroid conditions, such as Graves’ disease and Hashimoto’s disease, demonstrate a strong hereditary component, with research identifying major susceptibility loci involved in their development[2]. These studies reveal genetic heterogeneity, meaning different genetic variations can contribute to similar disease phenotypes, and highlight the importance of gene-gene interactions in determining individual risk. Furthermore, the overall regulation of the pituitary-thyroid axis, which controls thyroid hormone production, is under significant genetic influence[1].
Beyond specific diseases, genetic factors broadly impact the variation in thyroid hormone levels within populations[9]. Early familial studies also provided evidence for a hereditary basis in autoimmune thyroiditis, underscoring the role of inherited predispositions in developing thyroid disorders [3]. These findings collectively suggest that an individual’s genetic makeup is a fundamental determinant of their susceptibility to various thyroid diseases and the overall function of their thyroid system.
Environmental Factors and Their Role
Section titled “Environmental Factors and Their Role”Environmental factors contribute significantly to the variation observed in thyroid hormone levels among individuals[9]. While specific environmental triggers like diet, exposure to certain substances, or geographic influences are not detailed in all studies, their collective impact is recognized as an important modulator of thyroid function. These external elements can interact with an individual’s biological systems, potentially influencing the synthesis, metabolism, or action of thyroid hormones, thereby contributing to the development or exacerbation of thyroid conditions.
Interplay of Genes and Environment
Section titled “Interplay of Genes and Environment”Thyroid disease development and the regulation of thyroid hormone levels are not solely determined by genetics or environment, but rather by complex interactions between the two[9]. Research indicates that both genetic and environmental influences conjointly affect thyroid hormone variation, suggesting that an individual’s inherited predispositions can be modulated or triggered by specific environmental exposures. This dynamic interplay means that a genetic susceptibility may only manifest as disease under certain environmental conditions, highlighting the need to consider both intrinsic and extrinsic factors in understanding thyroid health.
Biological Background
Section titled “Biological Background”Thyroid disease encompasses a range of conditions that affect the thyroid gland, a crucial endocrine organ responsible for producing hormones vital for regulating metabolism, growth, and energy balance throughout the body. These conditions can result from complex interactions between genetic predispositions, immune system dysregulation, and environmental factors, leading to disruptions in normal physiological processes.
Thyroid Gland Function and Hormonal Regulation
Section titled “Thyroid Gland Function and Hormonal Regulation”The thyroid gland produces hormones that are essential for maintaining the body’s metabolic homeostasis. This critical function is tightly regulated by the pituitary-thyroid axis, a sophisticated feedback loop involving the pituitary gland and the thyroid gland [1]. The pituitary gland releases thyroid-stimulating hormone (TSH), which in turn stimulates the thyroid to produce and release thyroid hormones. Variations in these thyroid hormone levels, whether too high or too low, can disrupt numerous cellular functions and metabolic processes, impacting overall health[9]. The precise regulation of this axis is fundamental to preventing the systemic consequences associated with thyroid dysfunction.
Genetic Predisposition to Thyroid Disease
Section titled “Genetic Predisposition to Thyroid Disease”Genetic mechanisms play a significant role in an individual’s susceptibility to thyroid diseases. Familial studies have highlighted a strong hereditary component in conditions such as autoimmune thyroiditis, as well as Graves’ and Hashimoto’s diseases [3]. Research has identified major susceptibility loci associated with these familial autoimmune thyroid disorders, indicating specific genetic regions that contribute to disease risk[2]. The presence of genetic heterogeneity and gene interactions further complicates the inheritance patterns and phenotypic expression of these conditions, demonstrating how multiple genes can collectively influence disease development and severity[2]. Moreover, studies confirm a major genetic influence on the regulation of the pituitary-thyroid axis itself, suggesting that genetic factors can directly impact the fundamental control of thyroid hormone production[1].
Autoimmune Mechanisms in Thyroid Disorders
Section titled “Autoimmune Mechanisms in Thyroid Disorders”Many thyroid diseases, including autoimmune thyroiditis, Graves’ disease, and Hashimoto’s disease, are characterized by an autoimmune etiology. In these conditions, the body’s immune system mistakenly targets components of its own thyroid gland, leading to inflammation and dysfunction[3]. Graves’ disease typically results in overactivity of the thyroid (hyperthyroidism), while Hashimoto’s disease often leads to underactivity (hypothyroidism) due to progressive destruction of thyroid tissue. The familial clustering of Graves’ and Hashimoto’s diseases underscores a shared genetic susceptibility to these specific autoimmune processes that disrupt the thyroid’s normal cellular functions and hormone production[2].
Environmental and Genetic Interactions
Section titled “Environmental and Genetic Interactions”The development and progression of thyroid conditions are not solely determined by genetics but also involve a complex interplay with environmental factors. Studies have shown that both genetic and environmental influences contribute to variations in thyroid hormone levels within populations[9]. These interactions can modulate genetic expression and cellular pathways, impacting the thyroid gland’s function and the immune response against it. Understanding how genetic predispositions interact with specific environmental triggers is crucial for elucidating the full spectrum of pathophysiological processes that lead to thyroid disease and for developing targeted interventions.
Population Studies
Section titled “Population Studies”Population studies are fundamental to understanding the prevalence, incidence, and risk factors associated with thyroid disease across diverse groups. These large-scale investigations leverage extensive cohorts and advanced genetic methodologies to uncover both common and population-specific patterns of thyroid dysfunction.
Genetic Epidemiology and Thyroid Function Regulation
Section titled “Genetic Epidemiology and Thyroid Function Regulation”Population studies have significantly advanced understanding of the genetic underpinnings of thyroid function. A genome-wide association study (GWAS) specifically investigated genetic variants associated with serum TSH levels and overall thyroid function in a large cohort of 4,305 individuals selected from extensive family pedigrees, with TSH measurements available for 4,300 participants[6]. This study employed a comprehensive genotyping strategy using both 500K Affymetrix Mapping Array Set and 10K Mapping Array Set, allowing for efficient propagation of genotypes through pedigrees via imputation [6]. The findings identified phosphodiesterase 8B gene variants as significantly associated with serum TSH levels and thyroid function, highlighting a key genetic influence on this fundamental endocrine marker[6].
Beyond genetic analysis, the methodology included detailed phenotypic characterization; all participants underwent thyroid ultrasound examinations to assess gland size, echotexture, and volume, along with identifying conditions like goiter or chronic thyropathies[6]. Researchers also gathered records on self-reported thyroid disease statuses, including autoimmune thyroiditis, thyroid cancer, and prior surgeries, alongside hormone-replacement therapy usage[6]. Such detailed clinical phenotyping, combined with large-scale genetic data, is crucial for unraveling the complex interplay of genetic and environmental factors in thyroid disease prevalence and incidence within populations.
Large-Scale Cohort Studies and Longitudinal Observations
Section titled “Large-Scale Cohort Studies and Longitudinal Observations”Large-scale cohort studies are instrumental in understanding the long-term patterns and epidemiological associations of complex conditions like thyroid disease within populations. While specific thyroid findings from all major cohorts are not detailed, studies such as the Framingham Heart Study and the British 1958 Birth Cohort exemplify the robust design necessary for longitudinal investigations[10]. These cohorts, comprising thousands of participants, enable researchers to track health outcomes over decades, providing invaluable insights into incidence rates, prevalence patterns, and the evolution of disease over time[10]. The strength of such extensive, well-characterized populations lies in their ability to capture temporal changes and identify demographic factors and socioeconomic correlates influencing health trajectories.
The methodologies employed in these large cohorts often include extensive data collection on lifestyle, environmental exposures, and biological samples for biobank studies, facilitating comprehensive genome-wide association studies (GWAS)[5]. Such GWAS, involving thousands of cases and controls, are critical for identifying genetic risk variants that contribute to various diseases, including those affecting thyroid function[5]. The representativeness of these large sample sizes enhances the generalizability of findings to broader populations, though specific population characteristics must always be considered when interpreting results across diverse geographic and ethnic groups.
Cross-Population Genetic Comparisons and Methodological Considerations
Section titled “Cross-Population Genetic Comparisons and Methodological Considerations”Understanding how genetic and environmental factors influence thyroid disease prevalence and presentation across different populations is a crucial area of population studies. Research utilizing isolated founder populations, such as the one from the Pacific Island of Kosrae, offers unique opportunities to identify genetic risk variants due to reduced genetic heterogeneity[7]. This approach highlights how studying distinct populations can reveal population-specific genetic effects and potentially novel susceptibility loci relevant to complex traits [7]. Such comparisons are vital for understanding ancestry differences and geographic variations that may lead to different prevalence patterns or responses to treatments for thyroid conditions.
When conducting cross-population comparisons, methodological considerations regarding sample sizes, representativeness, and potential confounding factors are paramount. Genetic studies often involve collaborations across multiple international institutions to achieve diverse population representation, as seen in the extensive list of contributors to various genome-wide association studies [11]. This collaborative approach helps to improve the generalizability of findings, but also necessitates careful consideration of potential biases arising from varying environmental exposures, dietary habits, and healthcare access that might influence thyroid health outcomes across different ethnic and geographic groups.
Frequently Asked Questions About Thyroid Disease
Section titled “Frequently Asked Questions About Thyroid Disease”These questions address the most important and specific aspects of thyroid disease based on current genetic research.
1. My mom has thyroid problems; will I get them?
Section titled “1. My mom has thyroid problems; will I get them?”Yes, there’s a strong likelihood. Thyroid conditions like Hashimoto’s and Graves’ disease often run in families due to a significant genetic predisposition. While not guaranteed, having a close relative with thyroid disease increases your own risk because you share common genetic factors that influence thyroid function. It’s wise to discuss this family history with your doctor for appropriate monitoring.
2. Why do I feel so tired when others don’t?
Section titled “2. Why do I feel so tired when others don’t?”Your energy levels are heavily influenced by your thyroid hormones, which are partly regulated by your genes. Genetic factors can affect how your body produces and uses these hormones, leading to variations in energy metabolism. Even with similar lifestyles, genetic differences can make some individuals more prone to fatigue if their thyroid isn’t functioning optimally.
3. Why is my thyroid condition harder to manage than my friend’s?
Section titled “3. Why is my thyroid condition harder to manage than my friend’s?”Managing thyroid conditions can differ significantly between individuals due to genetic variations. These genetic factors influence how your body responds to treatment and how well your thyroid hormone levels are regulated. The complex interplay of your unique genetic makeup and other lifestyle factors can make your condition more challenging or responsive to therapy.
4. Can eating certain foods trigger my thyroid issues?
Section titled “4. Can eating certain foods trigger my thyroid issues?”While genetics primarily determine your susceptibility to thyroid disease, environmental factors, including diet, can interact with your genes. For those with a genetic predisposition, certain foods or nutritional deficiencies might influence the onset or severity of symptoms. However, the direct causal link between specific foods and triggering genetically-based thyroid issues is still an area of ongoing research.
5. Does stress worsen my thyroid if it runs in my family?
Section titled “5. Does stress worsen my thyroid if it runs in my family?”Yes, stress can potentially interact with your genetic predisposition to thyroid disease. While genetics lay the groundwork for susceptibility, stress is a known environmental factor that can influence the immune system and hormone regulation. For individuals with a family history, chronic stress might exacerbate existing thyroid conditions or even contribute to their development, highlighting gene-environment interactions.
6. Does my family’s heritage affect my thyroid risk?
Section titled “6. Does my family’s heritage affect my thyroid risk?”Yes, your ethnic or ancestral background can influence your risk for thyroid disease. Genetic variations and the prevalence of specific conditions can differ across populations. Research has shown that findings in one population may not directly translate to another, suggesting that certain ethnic groups might have unique genetic susceptibilities or protective factors.
7. Should my children be screened early for thyroid disease?
Section titled “7. Should my children be screened early for thyroid disease?”If thyroid disease runs in your family, early screening for your children might be beneficial. Given the strong genetic predisposition for conditions like autoimmune thyroiditis, knowing your family history allows for improved risk assessment. Discussing this with your pediatrician can help determine appropriate monitoring or early diagnostic strategies tailored to their genetic risk.
8. Why did I develop thyroid disease despite a healthy lifestyle?
Section titled “8. Why did I develop thyroid disease despite a healthy lifestyle?”Even with a healthy lifestyle, genetic factors can significantly predispose you to thyroid disease. While diet and exercise are crucial for overall health, your genes play a major role in regulating your thyroid function and immune system. Sometimes, a strong genetic susceptibility means that despite your best efforts, the underlying genetic architecture leads to disease development.
9. Why don’t thyroid medications work the same for everyone?
Section titled “9. Why don’t thyroid medications work the same for everyone?”The effectiveness of thyroid medications can vary due to individual genetic differences. Your unique genetic makeup influences how your body processes and responds to medications, affecting absorption, metabolism, and receptor sensitivity. This genetic variability contributes to why some people require different dosages or types of treatment for optimal thyroid hormone regulation.
10. Is feeling cold all the time a sign of genetic thyroid issues?
Section titled “10. Is feeling cold all the time a sign of genetic thyroid issues?”Feeling cold frequently can be a symptom of an underactive thyroid, and thyroid function has a strong genetic component. Genetic factors influence your body’s metabolism and temperature regulation through thyroid hormones. If this symptom is persistent and runs in your family, it could indicate a genetic predisposition to thyroid dysfunction, warranting a medical check-up.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
Section titled “References”[1] Hansen, P. S. et al. “Major genetic influence on the regulation of the pituitary-thyroid axis: a study of healthy Danish twins.” J Clin Endocrinol Metab, vol. 89, 2004, pp. 1181-1187.
[2] Tomer, Y. et al. “Mapping the major susceptibility loci for familial Graves’ and Hashimoto’s diseases: evidence for genetic heterogeneity and gene interactions.” J Clin Endocrinol Metab, vol. 84, 1999, pp. 4656-4664.
[3] Hall, R., and J. B. Stanbury. “Familial studies of autoimmune thyroiditis.” Clin Exp Immunol, vol. 2, 1967, p. Suppl-25.
[4] Burgner, D. et al. “A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease.”PLoS Genet, vol. 5, no. 1, 2009, e1000319.
[5] Wellcome Trust Case Control Consortium. “Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.” Nature, 2007. PMID: 17554300.
[6] Arnaud-Lopez, L. “Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid function.”American Journal of Human Genetics, vol. 82, no. 6, 2008, pp. 1270-1280.
[7] Lowe, J. K. et al. “Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.” PLoS Genet, vol. 5, no. 2, 2009, e1000365.
[8] Gudmundsson, J., et al. “Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations.”Nat Genet, vol. 41, 2009, pp. 460-464.
[9] Samollow, P. B. et al. “Genetic and environmental influences on thyroid hormone variation in Mexican Americans.”J Clin Endocrinol Metab, vol. 89, 2004, pp. 3276-3284.
[10] Franke, A., et al. “Systematic association mapping identifies NELL1 as a novel IBD disease gene.”PLoS One, 2007. PMID: 17684544.
[11] Melzer, D., et al. “A genome-wide association study identifies protein quantitative trait loci (pQTLs).” PLoS Genet, 2008. PMID: 18464913.