Genetic predisposition to MG raises risk for Graves’ disease, Hashimoto’s
Proactive treatment may help mitigate risk in affected patients, researchers say
People who are genetically predisposed to myasthenia gravis (MG) are more likely to develop Graves’ disease and Hashimoto’s thyroiditis, two autoimmune diseases of the thyroid gland, according to a study in China.
Researchers also found a genetic link in the opposite direction, where being genetically predisposed to Graves’ disease or autoimmune hypothyroidism — when the thyroid gland becomes underactive — increased the likelihood of developing MG.
“Further research is needed to investigate the complex mechanisms of this interrelationship, which could provide potential target genes and pathways for future disease treatment,” researchers wrote.
The study, “Association of Myasthenia Gravis With Autoimmune Thyroid Disease: A Bidirectional Mendelian Randomization Study,” was published in Brain and Behavior.
MG is an autoimmune disease that causes weakness and fatigue, mainly in the skeletal muscles used for movement, including those that control the eyes and eyelids. MG often occurs alongside other autoimmune diseases, including autoimmune thyroid diseases.
Genetic overlaps between MG and other autoimmune diseases
While the causal relationship between these disorders is unclear, “studies have identified genetic overlaps between MG and other autoimmune diseases, with thyroid abnormalities being the most notable,” the researchers wrote. The thyroid is a gland in the neck that regulates the body’s metabolism.
Autoimmune thyroid diseases occur when lymphocytes, white blood cells that normally help defend the body against infections, go awry and mistakenly attack the thyroid gland. The most common are Graves’ disease, which makes the thyroid overly active, and Hashimoto’s thyroiditis, where the thyroid is underactive.
To clarify if MG can cause autoimmune thyroid diseases, researchers turned to Mendelian randomization, a method that uses genetic information to find out if there is a causal link between an exposure (in this case, MG) and an outcome (autoimmune thyroid diseases).
The study drew on genetic data from 1,873 patients diagnosed with MG, who were matched to 36,370 healthy individuals of similar age and sex. Genetic data from patients with autoimmune hyperthyroidism (an overactive thyroid) or hypothyroidism, Graves’ disease, and Hashimoto’s thyroiditis came from a Finnish database.
When the researchers looked at genetic variants with a known link to these autoimmune diseases, they found patients who were genetically predisposed to MG had a 23.8% higher risk of developing Graves’ disease and a 24.2% higher risk of developing Hashimoto’s thyroiditis.
MG also linked to autoimmune hypothyroidism
MG was also linked to a small increase, by 3.7%, in the risk of developing autoimmune hypothyroidism. No significant genetic link was found between MG and autoimmune hyperthyroidism.
Reverse analysis revealed that genetic predisposition to autoimmune hypothyroidism was associated with a 20.5% increased risk of developing MG. Genetic predisposition to Graves’ disease also was associated with a 12.9% increased risk of developing MG. No genetic link was found for autoimmune hyperthyroidism or Hashimoto’s thyroiditis.
For patients 40 and younger with early-onset MG, the odds of developing Hashimoto’s thyroiditis were significantly increased by 7.3%. However, reverse analysis didn’t show that Hashimoto’s thyroiditis increases the odds for early-onset MG. No genetic link was found for patients with late-onset MG.
“Our research suggested the clinical importance of considering the possibility of comorbidities [coexisting diseases], advocating for appropriate routine screening to facilitate early prevention, detection, and treatment,” the researchers wrote.
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