A single gene that may play a key role in human intelligence is also the cause of a devastating brain disease that impedes mobility and diminishes cognitive thinking, according to research conducted at the University of Iowa.

Peg Nopoulos, MD, chair of psychiatry and UI professor of psychiatry, neurology, and pediatrics, has devoted her career to studying and treating Huntington’s Disease (HD), a fatal and progressive illness. Over the last decade, Nopoulos and her lab have been looking into the gene that causes HD. The gene, called HTT, has specific DNA repetitions in it. If these repetitions are expanded beyond a certain threshold in an individual, then that person will develop HD at some point in their lifetime.

Although it may cause disease, the gene has also been shown to be critical for brain development and, within a normal range of repeats, appears to have a beneficial effect on cognitive functioning. In other words, within a specific range, a larger number of repeats is associated with higher IQ in a healthy population.

“That was really exciting to us and the results are the strongest to date in documenting genetic determinants of IQ,” Nopoulos said.

Even in an era of huge genomic discovery there has been little work done to find the genes most strongly associated with intelligence because no study has investigated repeat number variation in association with IQ, she added. 

Nopoulos’ lab brought in kids from the community and all over the country ranging from the ages of six to 24 years who have a genetic risk of developing HD. In her latest publication, “Effect of Trinucleotide Repeats in the Huntington’s Gene on Intelligence,” Nopoulos reported that the repeats appear to be beneficial for IQ, until they hit disease threshold, where IQ then diminishes with increasing longer repeats. The results of the study show that the gene might create both an advantage for human intelligence, but also cause disease and be detrimental to cognitive functioning.

“It’s very beneficial to a certain point, and then it becomes toxic to development,” Nopoulos said.

In their sample of over 300 children, those with the highest IQ were those that were just past the threshold to develop HD.  This means that these children develop the disorder later in life, but they are also be the brightest among their peers, she said. The study’s findings put into question how ability and liability may have come to an intersection in human evolution.

“The genes that were involved in higher IQ, or a more complex brain, were the genes that were probably chosen by nature to evolve apes to humans,” Nopoulos said. “This class of genes that cause brain diseases, might well be the genes that mother nature chose to grow a human brain.”

Although there is currently no cure for HD, the study findings may have major implications for new drug therapies. An emerging gene therapy, that knocks down the HD gene, is already making its way through safety and efficacy trials. Even with the momentum to find a cure for HD, it will be important to consider the effects the gene has on necessary brain development, Nopoulos said.