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The study found a genetic link between vitiligo and autoimmune thyroid diseases, but no similar link with autoimmune hepatitis or Graves' disease.
Vitiligo shares a positive bidirectional causal link with several autoimmune thyroid diseases, including autoimmune thyroiditis, autoimmune hyperthyroidism, and Graves' disease, according to a recent study published in Skin Research and Technology.1
However, no causal relationship was observed between autoimmune hyperthyroidism or Graves' disease in vitiligo following a reverse Mendelian randomization analysis.
Numerous prior studies have shown a frequent co-occurrence of vitiligo with autoimmune thyroid diseases, particularly Hashimoto's thyroiditis and Graves' disease.
A 2018 study published in the European Journal of Dermatology reported that the prevalence of thyroid disease is significantly higher among individuals with vitiligo compared to those without.2 In 2013, researchers found that the prevalence is approximately 3 to 8 times higher in individuals with vitiligo versus in those without.3
However, according to authors of the present study, this past research has often relied on epidemiological and observational methods. To address these limitations, researchers Chen et al employed the Mendelian randomization method to avoid biases from confounding factors and measurement errors, aiming to investigate whether there are genetic causal associations between vitiligo and autoimmune thyroid diseases.
The Mendelian randomization method follows 3 main assumptions: a relevance assumption (single nucleotide polymorphisms [SNPS] must be strongly associated with the exposure of interest), an independence assumption (SNPs should be independent of any confounding factors between exposure and outcome), and an exclusion restriction assumption (SNPs should only affect the outcome through the exposure without any alternative pathways).
The study used summary genetic association data from genome-wide association study (GWAS) databases. Vitiligo data was obtained from a meta-analysis of 3 GWAS datasets, including 4680 cases and 39586 controls of European descent. Additional data pertaining to autoimmune thyroid diseases, including autoimmune thyroiditis, autoimmune hyperthyroidism, and Graves' disease, was collected from the FinnGen database.
The study identified 53 SNPs as effective instrumental variables for vitiligo in the forward Mendelian randomization. In the reverse Mendelian randomization analysis, 4 SNPs for autoimmune thyroid diseases, 8 SNPs for autoimmune hyperthyroidism, and 16 SNPs for Graves' disease were extracted.
Mendelian randomization analysis revealed a positive causal relationship between vitiligo and autoimmune thyroid diseases. Vitiligo was linked to an increased risk of autoimmune thyroid diseases with an odds ratio of 1.17, autoimmune hyperthyroidism with a ratio of 1.12, and Graves' disease with a ratio of 1.13.
The study also found that autoimmune thyroid diseases had a significant causal effect on vitiligo with an odds ratio of 1.10. However, there was no significant evidence for the causal effects of autoimmune hyperthyroidism and Graves' disease on vitiligo.
According to researchers, the study's strengths include the use of bidirectional Mendelian randomization for reliable causal inference and the use of robust GWAS databases. However, potential limitations include the inability to adjust for age and gender, the exclusive use of European cohorts, and the lack of a GWAS database for thyroid-related antibodies.
"Considering the consistent epidemiological evidence and the genetic causal association between vitiligo and [autoimmune thyroid diseases], doctors should be aware of this potential risk and focus on regular screening and monitoring of thyroid function in patients with vitiligo, with the aim of proactively intervening in disease progression," according to study authors Chen et al. "Meanwhile, patients with [autoimmune thyroiditis] should be informed about the likelihood of developing secondary vitiligo."
They recommend that further investigation is needed to understand the pathogenic and biological mechanisms pertaining to the increased risk of autoimmune thyroid diseases in vitiligo and the increased risk of vitiligo in individuals with autoimmune thyroiditis. Such research, they note, could lead to the discover of new immune targets for intervening in the progression of these comorbidities.
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