The thyroid is a master regulator that controls many of your body’s systems. It is integrally involved in metabolism and helps maintain body temperature, heart rate, breathing, and body weight. [ref]
Your genes play a big role in how well your thyroid works and how your body produces and converts the different forms of thyroid hormone.
This article explains how the thyroid works and which genetic variants impact thyroid function. It lists the specific thyroid-related variants that you can check using your genetic raw data from 23andMe or AncestryDNA.
Thyroid hormone levels play a vital role in how you feel and in your overall health and wellbeing. A lot of people think of thyroid in terms of metabolism and weight, but your thyroid hormones also affect your body temperature, gut health, muscle energy, heart rate, skin health, bone health, and more.
Why is this important? In 2016, the #1 prescribed medication in the US was a thyroid medication (Synthroid) with 123 million people taking the drug.[ref]
Your body needs the right amount of the thyroid hormones, and at the right time. Hypothyroidism is caused by too little thyroid hormone; hyperthyroidism is caused by too much thyroid hormone.
If you have thyroid problems, learning which genetic variants you carry may be a way to shed some light on what is going on with your thyroid.
Knowing where your genetic susceptibilities lie can help you figure out (along with your doctor) the best way to solve the problem.
Symptoms of hypothyroidism include:
This system all starts in the brain, instead of the thyroid. The hypothalamus, a region in the brain, and the pituitary gland control the rate at which the thyroid gland produces and releases thyroid hormone.
TSH then travels to the thyroid gland to signal for the production of thyroxine (T4) and triiodothyronine (T3).
Iodine molecules are an essential part of the T4 and T3 hormones. Within the thyroid gland, there are specific transporters to move iodine (in the form of iodide) into the follicular cells where the T3 and T4 are produced. More on this in the genetics section below….
The balance of the two types of thyroid hormone (T4 and T3) is important.
The thyroid gland produces and releases more T4 than T3 – around 80% is T4. Enzymes can convert T4 to T3 in your tissues and organs. Too much of the active T3 in cells will cause enzymes to inactivate the T3 into reverse T3 (rT3).[ref]
Thyroid hormone levels are an intricate balance between the production of T4, conversion to T3, inactivation to rT3, TSH levels, and the feedback loops controlling TRH and TSH.
Within cells, the thyroid hormone crosses into the nucleus and binds to a thyroid hormone receptor. These receptors then control the transcription of specific genes. Essentially, they turn on a gene so that whatever protein that gene codes for gets made. [ref]
In different cell types, the thyroid hormone receptors (THR) are going to control the production of different proteins.
Going a little deeper: the thyroid hormone receptors in the cell nucleus don’t act alone. They are often bound with a retinoic acid receptor, which is activated by vitamin A. The thyroid hormone receptors also need zinc in the way that they bind to the DNA. This makes it important to have adequate vitamin A and zinc levels – along with enough thyroid hormone being produced. [ref]
Finally, let me throw in that there are actually two different thyroid hormone receptors – THR-alpha and THR-beta. While both are located in most types of cells, THR-beta is the major form in the liver and THR-alpha is the major form in the heart cells and the bone. [ref]
Graphical overview thyroid-related genes:
The basic thyroid test that most doctors run is the TSH (thyroid-stimulating hormone) level. Genetic variants in the TSH related genes are responsible for approximately 50 – 90% of thyroid hormone variability. [ref] Thus, you can be naturally higher or lower on TSH levels due to genetic variants.
The TSHR gene (thyroid-stimulating hormone receptor) codes for a receptor protein that controls thyroid cell metabolism [ref] TSH levels are tied to genetic variations of the TSHR gene.
Check your genetic data for rs1991517 D727E (23andMe v.4; AncestryDNA):
Members: Your genotype for rs1991517 is —.
Check your genetic data for rs121908866 (23andMe v4;AncestryDNA);
Members: Your genotype for rs121908866 is —.
Check your genetic data for rs121908867 (AncestryDNA);
Members: Your genotype for rs121908867 is —.
The PDE8B gene codes for a protein that causes the inactivation of cyclic AMP (important in energy regulation) in the thyroid. PDE8B genetic variants have been repeatedly associated with TSH levels, specifically in people of European background.[ref]
Check your genetic data for rs4704397 (23andMe v.4, v.5; AncestryDNA):
Members: Your genotype for rs4704397 is —.
Check your genetic data for rs6885099 (23andMe v.4, v.5; AncestryDNA)
Members: Your genotype for rs6885099 is —.
The FOXE1 gene (thyroid-specific forkhead transcription factor) has also been identified to increase the risk of primary hypothyroidism[ref] and with changes in TSH levels.
Check your genetic data for rs7850258 (23andMe v.4, v.5; AncestryDNA):
Members: Your genotype for rs7850258 is —.
Check your genetic data for rs965513 (23andMe v.4, v.5, AncestryDNA):
Members: Your genotype for rs965513 is —.
DIO1 & DIO2 genes: The deiodinase 1 (DIO1) gene encodes a protein that converts T4 to T3 and is involved in the degradation of both T3 and T4 in the liver, kidney, thyroid, and pituitary gland. Iodine and selenium are involved in these reactions.[ref] DIO2 is also involved in the conversion of T4 to T3, mainly in the skeletal muscles, central nervous system, pituitary, thyroid, heart, and brown fat.[ref]
Check your genetic data for rs2235544 (23andMe v4, v5; AncestryDNA):
Members: Your genotype for rs2235544 is —.
Check your genetic data for rs11206244 (23andMe v4, v5; AncestryDNA):
Members: Your genotype for rs11206244 is —.
Check your genetic data for rs225014 (23andMe v.4; AncestryDNA):
Members: Your genotype for rs225014 is —.
Graves’ disease is an autoimmune condition that affects about 1% of the population and causes hyperthyroidism. In Graves’ disease, the body produces antibodies against TSHR.
Hashimoto’s disease is an autoimmune condition that causes hypothyroidism. The prevalence of Hashimoto’s in Caucasian women is between 1-2%. [ref]
Genetic variants in the TSHR gene influence the risk of the autoimmune thyroid diseases (AITD), which includes Graves’ disease and Hashimoto’s thyroiditis. It is estimated that about 80% of the risk for autoimmune thyroid disease is due to genetics (with environmental factors making up the rest of the risk).[ref][ref]
Check your genetic data for rs3783938 ( 23andMe v.4, AncestryDNA):
Members: Your genotype for rs3783938 is —.
Check your genetic data for rs12101255 ( 23andMe v.4, AncestryDNA):
Members: Your genotype for rs12101255 is —.
Check your genetic results for rs179247 (23andMe v4, AncestryDNA):
Members: Your genotype for rs179247 is —.
TPO Gene: Thyroid peroxidase (TPO) antibodies are a marker of autoimmune thyroid disease. Several genetic variants in the TPO gene are associated with an increased risk of autoimmune thyroid disease.
Check your genetic data for rs2071403 (23andMe v5; AncestryDNA.)
Members: Your genotype for rs2071403 is —.
The PTPN22 gene is associated with an increased risk of many autoimmune diseases, including Hashimoto’s.
Check your genetic data for rs2476601 (23andMe v4; AncestryDNA):
Members: Your genotype for rs2476601 is —.
THRB & THRA genes: The thyroid hormone receptor genes code for the receptor that the thyroid hormone binds to in the nucleus of the cell. Mutations in these genes (rare!) cause thyroid hormone resistance. Generally, THRB or THRA mutations will cause hypothyroidism that is recognized and diagnosed in infants or children.[ref] In other words, mutations cause more severe symptoms that affect growth and development.
Check your genetic data for rs28933408 (23andMe v4):
Members: Your genotype for rs28933408 is —.
Check your genetic data for rs137853162 (AncestryDNA only)
Members: Your genotype for rs137853162 is —.
SERPINA7 gene: codes for the thyroxine-binding globulin protein
Check your genetic data for rs28933689 (23andMe v4 only):
Members: Your genotype for rs28933689 is —.
Check your genetic data for rs2234036 (23andMe v4 only):
Members: Your genotype for rs2234036 is —.
If you are on thyroid medication or under the care of a doctor, please be sure to talk with your doctor about making any changes, including dietary changes, that could affect your thyroid hormone levels.
Selenium is essential to the conversion of T4 to T3. Brazil nuts are a good source of selenium, and supplements are also available.
Melatonin: The production of melatonin is regulated by TSH. Increasing melatonin increases thyroglobulin. The thyroid gland cells also synthesize melatonin. [ref] You can increase your melatonin levels naturally by blocking blue light at night or synthetically through taking melatonin at night.
Iodine: Make sure you get iodine in your diet – either through seafood, kelp, or iodized salt.
Myo-inositol For autoimmune thyroid problems, Myo-inositol and selenium have been shown to reduce antibody levels. [ref]
Vitamin D supplement has been shown to reduce Hashimoto’s antibody levels. [ref]
Gluten may be a problem for a few people: Gluten is often pointed to as a culprit in autoimmune thyroid diseases (Graves and Hashimoto’s). A 2003 study showed that ~5% of patients with autoimmune thyroiditis also had immune reactions to gluten. [ref] While that isn’t a huge percentage, it may be worth trialing a gluten-free diet if you have an autoimmune thyroid disease. The flip side of that is also worth noting — 95% of people with autoimmune thyroid disease may have no problem with gluten.
Eat your fruits and veggies: The dietary flavonoid kaempferol, found in apples, onions, leeks, grapes, and other fruits and vegetables, induces DIO2, increasing conversion to T3. [ref]
Avoid fasting: In studies, fasting and critical illnesses increase the levels of DIO3, which is the enzyme that deactivates thyroid hormone. [ref] Fasting (and illness!) may be hard on your supply of active thyroid hormone.
Blocking blue light: Light and circadian rhythms play a role in DIO3 expression as well. [ref] Blocking blue light in the evening (from LED bulbs, TV screens, etc) by wearing blue-blocking glasses will help to keep your circadian rhythm on track.
Blame mom: Several recent studies have also pointed to the hereditary epigenetic effects on DIO3 as well. [ref]
Studies on environmental toxins that impact thyroid function show:
updated and revised 6/2020