Eye with DNA strands, symbolizing genetic influence on eye health.

Decoding Thyroid Eye Disease: Is Genetics the Missing Piece?

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Rhea Morgan in Health & Wellness December 2025 • 4 min read.

"New research identifies a potential genetic link to thyroid-associated orbitopathy, offering hope for better understanding and treatment."


Thyroid Eye Disease (TED), also known as thyroid-associated orbitopathy (TAO), is an autoimmune condition where the immune system mistakenly attacks the tissues around the eyes. This can lead to a range of uncomfortable and disfiguring symptoms, from dry eyes and swelling to vision impairment and even blindness. Affecting up to 50% of individuals with Graves' disease, TED presents a significant challenge in both diagnosis and treatment.

While the link between Graves' disease and TED has been well-established, the precise genetic factors that determine who develops TED have remained elusive. Countless studies have explored various candidate genes, but the results have often been inconsistent, highlighting the complexity of the condition.

Now, an innovative genome-wide association study (GWAS) is shedding light on a potential genetic link to TED. For the first time, researchers have identified a specific gene, MACROD2, that may play a role in increasing susceptibility to TED in individuals with Graves' disease. This discovery could pave the way for more targeted treatments and a better understanding of the underlying mechanisms of this challenging condition.

Unraveling the Genetic Connection: What Does the MACROD2 Gene Do?

Eye with DNA strands, symbolizing genetic influence on eye health.

The study, published in Investigative Ophthalmology & Visual Science, was conducted by researchers across multiple institutions in Australia. The research team performed a genome-wide association scan (GWAS) on pooled DNA samples from Australian Caucasian participants, comparing individuals with Graves' disease and TED (cases) to those with Graves' disease but without TED (controls).

The initial GWAS revealed several single nucleotide polymorphisms (SNPs) – variations in a single point in the DNA sequence – that showed suggestive associations with TED. However, one SNP, rs6110809, located within the MACROD2 gene on chromosome 20p12.1, emerged as the most promising candidate. This particular SNP consistently associated with TED across both the discovery and replication cohorts.

  • Discovery Cohort: Included 265 participants with Graves' disease and TED (cases) and 147 patients with Graves' disease without TED (controls).
  • Replication Cohorts: Two additional cohorts totaling 584 cases and 367 controls were used to validate the initial findings.
  • GWAS on Pooled DNA: A cost-effective approach used to screen for gene variants associated with TED.
  • Individual Genotyping: Top-ranked SNPs were then genotyped in individual DNA samples to confirm the GWAS results.
Further analysis revealed that the minor A allele of rs6110809 was significantly more frequent in individuals with TED than in those with Graves' disease alone. This association remained significant even after adjusting for factors like age, sex, duration of Graves' disease, and smoking. This suggests that this genetic variation in MACROD2 may independently contribute to the development of TED in people already predisposed to Graves' disease.

What's Next? Confirming the Link and Exploring New Treatments

The discovery of the MACROD2 association with TED opens up exciting new avenues for research and potential treatment strategies. While the study provides compelling evidence for a genetic link, it's essential to confirm these findings in additional independent cohorts with diverse ethnic backgrounds. Future research should also focus on elucidating the precise function of MACROD2 in the context of orbital tissues and its role in the inflammatory processes that drive TED. Ultimately, a deeper understanding of the genetic and molecular mechanisms underlying TED could lead to the development of targeted therapies that prevent or alleviate the debilitating symptoms of this condition, offering hope for improved quality of life for those affected.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

What is Thyroid Eye Disease (TED), and what are its common symptoms?

Thyroid Eye Disease (TED), also known as thyroid-associated orbitopathy (TAO), is an autoimmune condition. It occurs when the immune system mistakenly attacks the tissues around the eyes. This can lead to various symptoms, including dry eyes, swelling, vision impairment, and, in severe cases, even blindness. TED affects up to 50% of individuals with Graves' disease.

2

What role does Graves' disease play in the development of Thyroid Eye Disease (TED)?

Graves' disease and TED are linked, as TED commonly occurs in individuals with Graves' disease, an autoimmune condition that causes the thyroid gland to overproduce hormones. While the exact mechanisms aren't fully understood, the presence of Graves' disease increases the risk of developing TED. The article highlights that although the link is established, researchers are still exploring the specific genetic factors that determine who with Graves' disease will develop TED.

3

How did researchers identify the MACROD2 gene as potentially linked to Thyroid Eye Disease (TED)?

Researchers used a genome-wide association study (GWAS) to identify potential genetic links to TED. This involved comparing the DNA of individuals with Graves' disease and TED (cases) to those with Graves' disease but without TED (controls). The GWAS initially revealed several SNPs (single nucleotide polymorphisms). One specific SNP, rs6110809, located within the MACROD2 gene, emerged as the most promising candidate. This association was then validated across multiple cohorts, making the MACROD2 gene a key focus.

4

What is the significance of the MACROD2 gene in the context of Thyroid Eye Disease (TED), and how does its variation impact the disease?

The MACROD2 gene has been identified as potentially playing a role in increasing susceptibility to TED in individuals with Graves' disease. The study found that a specific variation in the MACROD2 gene, the minor A allele of rs6110809, was more frequent in individuals with TED. This association was significant even after considering factors like age, sex, and the duration of Graves' disease, suggesting that this genetic variation may independently contribute to the development of TED. The precise function of MACROD2 in orbital tissues and its role in inflammatory processes that drive TED need further research.

5

What are the next steps in research and potential implications for the treatment of Thyroid Eye Disease (TED) based on this new genetic finding?

The discovery of the MACROD2 gene association with TED opens new avenues for research. Future research involves confirming the findings in independent cohorts with diverse ethnic backgrounds and understanding the function of MACROD2 in orbital tissues and its role in the inflammatory processes that drive TED. A deeper understanding of the genetic and molecular mechanisms underlying TED could lead to targeted therapies that prevent or alleviate the debilitating symptoms of this condition. This could lead to improved quality of life for those affected by TED.

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