The Genetic Causes of Graves Disease: How Genes Contribute to Graves Disease Symptoms and More

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Graves Disease Definition

Graves disease is named after Irish doctor Robert James Graves who described the condition in 1835. The immune system produces antibodies to the receptor for thyroid-stimulating hormone (TSH) which sends the protein into overdrive and excessive quantities of thyroxine hormone are produced. This results in the thyroid gland increasing to more than twice its normal size. It tends to occur primarily in women aged 30-50 and is the most common cause of hyperthyroidism. If treated, the condition is rarely life-threatening

Graves Disease Symptoms

There are a range of Graves disease symptoms which can include one or more of the following; -

  • Increased appetite
  • Weight loss
  • Itching
  • Dislike of hot weather
  • Tremors
  • Diarrhoea
  • Fatigue
  • Muscular weakness
  • Eyes may appear to bulge as tissues and muscles behind the eyes swell.

Graves Disease Causes

Your immune system usually does a fine job of protecting you from viral and bacterial attack. it produces a whole arsenal of antibodies to tackle and eliminate these microbial pests. However, sometimes the body mistakenly turns on itself, and this is what is known as an autoimmune disease. In Graves disease antibodies are produced which attack the thyroid. Fortunately it is not destroyed in the process, but it does produce excessive amounts of thyroid hormone.

Graves Disease and Genetics

There are a number of known Graves disease (GD) risk factors including age, stress, smoking, and family history. That an individual’s susceptibility to Graves disease is heightened by having family members with the condition strongly suggests that there are genetic components involved in the production of antibodies to the thyroid-stimulating hormone receptor. It is highly likely that more than one gene will be involved, and for several years researchers have been on the hunt for them.

In 2007 scientists at UCLA’s Jules Stein Eye Institute and Harbor-UCLA Medical Center discovered a defect on T-cells. In GD patients the researchers observed that these immune cells had an abnormal surplus of the receptor that is targeted by the same antibody that does not recognize the thyroid gland as self. It is believed that this fault triggers the cell to keep growing long after it was meant to die. T-cells then accumulate in such numbers that the body then attacks itself.

Several susceptibility genes have been identified - CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22. Human leukocyte antigen (HLA) alleles have also been detected - there are different versions of these genes in GD and non-GD patients, and specific alleles will predispose a person to the autoimmune disease. HLA genes are found on chromosome 6 and the different alleles identified include DRB1-0304 and DQB1-02.

Vitamin D-binding protein gene (DGP) has also been linked with Graves disease. GD patients have less vitamin D in their blood than the average population and Pani et al discovered that a polymorphism of this gene (i.e. a genetic variant) is associated with susceptibility to Graves disease.

This is by no means an exhaustive list of possible contributory genetic factors. Many more have been discovered, although specific risk factor genes are still a mystery. The picture is also slightly complicated by the fact that Graves disease can also be triggered by environmental stressors such as viral or bacterial infection. Perhaps these microbes raise antibodies that then react with the TSH receptor on the thyroid gland.

As more is revealed at the molecular level scientists will gain a clearer picture as to why some people are susceptible to GD and others are not. Research will also hit upon genetic and metabolic pathways that could be key targets foe therapeutics. And as with all areas of medical science there is no delivery date; research is a long drawn out process, with each new discovery building on the last, as science moves ever closer toward more effective treatments and cures.


Jacobson EM, Tomer Y. The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: back to the future. J Autoimmun. Mar-May 2007;28(2-3):85-98.

Pani et al. A Polymorphism within the Vitamin D-Binding Protein Gene Is Associated with Graves’ Disease but Not with Hashimoto’s Thyroiditis. J. Clin. Endocrinol. Metab., Jun 2002; 87: 2564 - 2567.