In the largest study of its kind, scientists identified more than 100 genes linked to thyroid disease. Researchers used this genomic data to identify people at high risk for developing thyroid problems and the age at which their diseases would manifest.
“It greatly improves our understanding of the genetic architecture of thyroid function and thyroid disease,” he said John Walsch (opens in new tab), a clinical professor at the University of Western Australia Medical School who was not involved in the study. The new study, which has yet to be peer-reviewed, was published in the preprint database on December 22 medRxiv (opens in new tab).
the thyroid is a butterfly-shaped organ in the throat that releases hormones essential to controlling how cells convert nutrients and oxygen into energy. People with hyperthyroidism have an overactive thyroid, which produces excessively high levels of these hormones. Those with an underactive thyroid, or hypothyroidism (opens in new tab)do not produce enough thyroid hormones.
The conditions cause some of the same symptoms, including fatigue and muscle weakness, but differ in different ways; For example, hyperthyroidism can lead to weight loss and irregular heartbeats, while hypothyroidism can lead to weight gain and constipation.
Related: Seven possible signs of an underactive thyroid
Factors that increase the risk of thyroid disease include being over the age of 60, smoking and an inadequate diet iodine. And past studies have certainly shown that Genes predispose people to both autoimmune thyroid disorders (opens in new tab) and other autoimmune diseases, such as type 1 diabetes. But genes that specifically affect thyroid function are less well understood. To gain a better understanding, scientists analyzed the genomes of nearly 250,000 people of European descent.
They looked for differences in the genomes of people with different levels of a hormone strongly linked to thyroid disease, called thyroid-stimulating hormone (TSH). TSH is produced by the pituitary gland in the brain and controls the amount of hormones produced by the thyroid. With an overactive thyroid, the body tries to lower thyroid hormone levels by keeping TSH levels low, but the organ continues to produce hormones. In hypothyroidism, the brain produces high levels of TSH to increase thyroid hormone levels, but the thyroid fails to produce enough hormones in response.
In their analysis, the scientists identified 112 genes that could influence the TSH level and thus the risk of thyroid disease. Of those 112 genes, 78 had never been associated with TSH levels before.
Some of the genes newly linked to TSH levels are involved in blood vessel growth and nerve cell survival. More work is needed to understand exactly how these processes contribute to thyroid disease. “The hope is that with a better understanding of how thyroid disease develops, new therapeutic targets can be identified,” Walsh said.
Revealing how genetics influence risk of thyroid disorders could also allow doctors to predict who is most at risk of developing the disorders. This could enable high-risk patients to better manage their lifestyle to reduce the risk of the disease, for example by avoiding smoking, reducing alcohol consumption or eating foods rich in iodine.
To test this idea, the researchers used their new understanding of TSH-related genes to predict people’s risk for hyperthyroidism and hypothyroidism. They generated “risk scores” for hundreds of people of European descent, some of whom had thyroid disease. By comparing people’s risk scores to actual cases of thyroid disease, the team found that their risk scores predicted people’s risk of the disease fairly accurately.
These scores reflected a sliding scale of risk, with those with the highest scores more likely to have hypothyroidism and those with the lowest scores more likely to have hyperthyroidism. This is not to say that someone with a low score cannot develop hypothyroidism; You just have less of a chance than someone with a high score.
Specifically, the study found that nearly 18% of people in the top 10% of scores had developed hypothyroidism by age 80, compared to just 5% of people in the bottom 10% of scores. For hyperthyroidism, the opposite trend was seen: nearly 4% of people in the lowest 10% scores developed hyperthyroidism by age 80, compared with just 1% of people in the top 10% scores.
The risk scores could also predict when people would likely develop thyroid disease. For example, people with the highest scores typically developed hypothyroidism by age 51, while those with the lowest scores who developed the condition did not do so until age 75.
A limitation of the study is that these risk assessments were created for individuals whose genomic data contributed to the original data set used to locate TSH-related genes. Ideally, the risk assessments would be tested on an independent sample of people. To do this, the scientists later tested the risk scores on an independent group of people and found that they worked similarly well; these dates will be published shortly.
While such risk assessments could prompt those at high risk to make beneficial lifestyle changes, genetic testing is unlikely to replace current diagnostic tools. “Screening for thyroid disease with a TSH measurement is cheap and easy, it’s hard to imagine genetic profiling will replace it,” Walsh told Live Science.
Scientists also need to study more diverse ancestors to prevent such genetic testing from increasing health inequalities. “To understand the genetic architecture of thyroid disorders within and between ancestors, larger sample sizes are needed in non-European ancestors,” the team wrote in their article.