A Yale-led international team of researchers took the first step in identifying genetic factors in Obsessive-Compulsive Disorder (OCD).

According to Dr. Thomas Fernandez, Assistant Professor in the Yale Child Study Center and Department of Psychiatry who led the team, very little research has been done into the genetics of OCD. The treatments have changed little in the past two or three decades, even as treatments for other persistent mental and behavioral diagnoses have multiplied. “We decided to follow one method that proved fruitful in autism genetic research, namely, looking at de novo mutations,” he said. De novo spontaneous mutations that are not inherited from parents.

Partnering with Euripedes C. Miguel and the psychiatrists at the Institute of Psychiatry in Sao Paulo, Brazil, they identified 20 families where the parents have no symptoms, and the children are diagnosed with OCD. These families are popular for genetic research, because it is likely that the children have new mutations of genes intimately involved in OCD.

The 1.5% of the genome that codes for genes, called the exome, of the parents and children was compared to the general population to see if there was a difference in the rate of de novo mutations. The first question to answer, said Fernandez, is “are there more de novo mutations in the OCD population than in the general population?” If the answer is yes, it sets the stage for extensive sequencing.

The pilot group of OCD subjects showed a significantly higher rate of de novo mutations, providing the rationale for larger sequencing efforts. “Currently we are sequencing 200 families,” says Fernandez. The larger sample will allow for analysis of patterns among the mutations, such as networks of genes with common biological functions.

Further research also analyzes a larger proportion of the genome, including regulatory functions, which were left out of the pilot.