Science in Mind

Some genes may thwart disease

The search for genes that cause diseases has become one of modern medicine’s major quests. Studies of DNA from thousands of people have revealed genes that underlie illnesses as varied as type 2 diabetes, Alzheimer’s, and rare musculoskeletal conditions.

But scientists know that genes may not only make us susceptible to diseases; they may also protect us from them.

The problem is that the methods for finding protective genes have been less obvious, and the hunt for them less intense. A study published last week by a University of Massachusetts Medical School researcher suggests that a genetic form of dwarfism frequently found in a population of the Old Order Amish of Pennsylvania protects against bipolar disorder. That finding, scientists believe, could eventually lead to a new approach to treating the disease.


Sporadic reports over the years have revealed that people with genetic mutations are sometimes protected from common diseases.

For example, people with Down syndrome appear to be protected against some kinds of cancer; they rarely develop deadly tumors. A small population from Northern Italy has been found to carry a mutated protein that protects them against heart disease. A rare form of dwarfism found in individuals from Ecuadorian villages protects against diabetes and cancer.

Probing the genetic mutations that are protective may help scientists understand how these diseases are caused at the molecular level — and aid in the creation of drugs that have a similar effect as the genetic mutation.

Naturally, researchers don’t want a drug that will repeat what each disease does exactly. Instead, they hope to glean clues about how the genetic mutations that cause dwarfism prevent mental illness from developing in afflicted individuals. Those lessons could then be used to design more effective treatments for broader populations.

“What has happened is the pieces of the puzzle came together more recently over the last several months,” said Dr. Edward Ginns, a neurologist at UMass Medical School and the senior author of the paper published in Nature Molecular Psychiatry. “What we are reporting is that here’s the phenomena that this rare genetic disorder, the mechanism in it which was not obvious years ago, that actually protects those individuals from getting bipolar disorder.”


A rare, genetic form of dwarfism called Ellis-van Creveld is relatively common among the Old Order Amish of Pennsylvania. The researchers were intrigued by the fact that over four decades of study, no individuals in the community had been reported with both dwarfism and bipolar disorder, which is also common. They did a statistical analysis that showed this pattern was unlikely to be due to chance.

Then, the researchers began to scrutinize the rare form of dwarfism, which is caused by disruption to a particular molecular pathway. That pathway, called sonic hedgehog, has been studied carefully over the years because of the role it plays in early development and cancer, but it had not been implicated in bipolar disorder. That sparked their curiosity.

Now, the researchers plan to look more precisely for the mutations that could underlie the protective effect so they can examine its function in laboratory tests and in laboratory animals. They will look in broader populations of people with and without bipolar disorder to see if alterations in the genes that are involved in the pathway show similar patterns as the cases in the Amish community.


Those types of experiments will be necessary to show that the protection they observe is truly caused by the mutation. Ginns said that since inhibitors of those molecules are already in development as cancer treatments, it should also be relatively easy to set up a clinical trial to see if the drugs work against bipolar disorder or other mental illnesses.

Carolyn Y. Johnson can be reached at cjohnson@globe.com. Follow her on Twitter @carolynyjohnson.