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FOXE1 and Thyroid Health: What Your rs965513 Genotype Means

The thyroid gland produces hormones that regulate metabolism, energy, mood, and reproductive health. The FOXE1 gene helps guide thyroid development and ongoing function by controlling expression of other genes in thyroid tissue. A common genetic variant near FOXE1, called rs965513, influences thyroid-stimulating hormone (TSH) levels and is associated with differences in thyroid regulation and cancer risk.

This article explains how different rs965513 genotypes can affect thyroid health, symptoms to watch for, and practical steps you can take through diet, lifestyle, monitoring, and screening to support long-term wellness. PlexusDx does not provide medical advice. Always consult your healthcare provider before making medical or major lifestyle decisions.

How the FOXE1 rs965513 Variant Affects Thyroid Function

TSH is released from the pituitary gland and signals the thyroid to make thyroid hormones. Variants near FOXE1 can shift the set point for TSH and thyroid hormones. People with the A allele at rs965513 tend to have lower TSH levels, which often reflects relatively higher circulating thyroid hormone or a tendency toward subclinical hyperthyroidism. This can influence metabolism, heart rate, menstrual cycles, bone health, and long-term cancer risk.

2 effect alleles (AA) — decreased TSH, higher thyroid activity risk

Genotype: AA (two copies of the effect allele)

What this means: With AA at rs965513 you are more likely to have decreased TSH levels, indicating a genetic predisposition toward relatively higher thyroid hormone activity or an altered regulatory set-point. This pattern is associated with a higher lifetime risk of thyroid cancer compared with the non-effect genotype. Over time you may be more prone to subtle hyperthyroid tendencies.

Possible signs and health impacts:

  • Faster resting heart rate or palpitations
  • Heat intolerance or increased sweating
  • Unexplained weight loss or increased metabolism
  • Menstrual irregularities or changes in fertility
  • Long-term risk for reduced bone mineral density if unrecognized
  • Small increased lifetime risk for thyroid cancer

Recommended actions:

  • Ask your provider for regular thyroid function tests: TSH, free T4, and free T3
  • Discuss thyroid ultrasound or specialist referral if nodules, family history, or persistent abnormal tests occur
  • Maintain balanced iodine intake — avoid excessive iodine supplements unless advised
  • Include selenium-rich foods (for example, Brazil nuts in moderation) to support thyroid antioxidant systems
  • Ensure adequate vitamin A, zinc, and iron from diverse food sources to support thyroid hormone synthesis and transport
  • Monitor bone health over time and discuss bone density screening with your clinician if indicated
  • Reduce exposure to environmental toxins when possible and maintain consistent meal timing to support hormonal balance
1 effect allele (AG) — likely decreased TSH, intermediate risk

Genotype: AG (one copy of the effect allele)

What this means: AG is associated with a likely decrease in TSH, suggesting your thyroid may produce relatively higher thyroid hormone levels compared with the GG genotype. The AG genotype carries a modestly increased risk of thyroid cancer compared with GG.

Possible signs and health impacts:

  • Mild hyperthyroid-like symptoms such as occasional palpitations or heat sensitivity
  • Potential subtle shifts in menstrual cycle regularity
  • Small potential effects on metabolism and long-term bone health if not monitored

Recommended actions:

  • Request routine thyroid function testing (TSH, free T4, free T3) as part of periodic health checks
  • Consider thyroid ultrasound or specialist consultation if you have nodules, persistent symptoms, or family history
  • Balance iodine intake — consume iodized salt in moderation and avoid high-dose iodine supplements unless recommended
  • Eat selenium-containing foods such as Brazil nuts, seafood, or seeds to support thyroid antioxidant enzymes
  • Include dietary sources of vitamin A, zinc, and iron such as leafy greens, lean meats, legumes, and fortified foods
  • Keep lifestyle habits that support hormonal stability: regular sleep, stress management, and consistent meals
0 effect alleles (GG) — typical TSH, standard risk

Genotype: GG (two copies of the non-effect allele)

What this means: GG is associated with typical thyroid hormone regulation and standard TSH levels for this specific genetic site. This genotype is not linked to the lowered TSH or increased thyroid cancer risk associated with the A allele at rs965513.

Possible signs and health impacts:

  • Thyroid function is likely to be within expected ranges based on this variant
  • Standard population-level risk for thyroid cancer related to this site

Recommended maintenance steps:

  • Continue routine health checks that include thyroid testing as recommended by your provider
  • Support thyroid health with balanced iodine, selenium-rich foods, and adequate vitamin A, zinc, and iron
  • Maintain healthy lifestyle habits: balanced diet, regular activity, stress management, and avoiding environmental toxins

Diet and Supplement Considerations

Balanced nutrition supports healthy thyroid function. Key nutrients include iodine, selenium, iron, zinc, and vitamin A. Aim to get these primarily from food. Examples:

  • Iodine: iodized salt in moderation, sea vegetables and seafood. Avoid high-dose iodine supplements unless prescribed.
  • Selenium: Brazil nuts (1 to 2 nuts several times per week), seafood, eggs, and seeds.
  • Iron: red meat, poultry, lentils, spinach. Treat iron deficiency if present since it can impair thyroid hormone production.
  • Zinc: oysters, beef, legumes, pumpkin seeds.
  • Vitamin A: liver in small amounts, sweet potatoes, carrots, dark leafy greens, and fortified foods.

If you are considering supplements, discuss doses with your healthcare provider to avoid excess intake, particularly iodine and selenium, which can be harmful at high levels.

Lifestyle and Monitoring Recommendations

  • Screening and monitoring: Ask your provider about baseline and periodic TSH, free T4, and free T3 testing. If you have symptoms or a family history, consider thyroid ultrasound or referral to an endocrinologist.
  • Bone health: Because untreated hyperthyroidism can affect bone density, discuss bone health monitoring if tests suggest persistent high thyroid hormone activity.
  • Avoid environmental exposures that may affect thyroid function such as certain industrial chemicals and excessive iodine from non-food sources when possible.
  • Maintain consistent meal timing and healthy sleep to support hormone balance.
  • Manage stress through regular exercise, sleep hygiene, and relaxation practices to reduce impacts on the endocrine system.

When to Talk to Your Healthcare Provider

  • If you experience persistent palpitations, unexplained weight change, heat intolerance, or irregular menstrual cycles
  • If routine thyroid tests are abnormal or show suppressed TSH
  • If you notice a lump in your neck, difficulty swallowing, or persistent hoarseness
  • If you plan to start supplements that contain iodine or high-dose selenium

PlexusDx does not provide medical advice. This information is educational and describes genetic predispositions related to the FOXE1 rs965513 variant. Always consult your healthcare provider to interpret your results in the context of your medical history, symptoms, and other risk factors before making health decisions.