May 20, 2026 — In the largest-ever study into the genetics of obsessive-compulsive disorder, researchers have identified multiple DNA variants that could help predict who is at greater risk of developing the psychiatric disorder — and guide better ways to treat it.

While previous studies have shown that OCD can run in families, this is the first time researchers have made substantial progress in identifying genetic-risk loci, the specific locations on a chromosome where DNA variants are associated with higher susceptibility of a specific disease or trait. Thirty independent loci were found, with 25 genes in those loci likely contributing to OCD risk.

Co-led by Carol Mathews, M.D., chair of the UF College of Medicine’s Department of Psychiatry, the study by over 200 investigators across the world is the culmination of more than 20 years of sample collection.

That collection is now the largest-ever genome-wide association study of OCD, with 53,660 OCD cases and over 2 million controls. Findings were reported May 13 in the journal Nature Genetics.

“When we started early in my career, we were looking for genes that cause OCD. We thought back then that it would be one or two,” said Mathews, director of UF’s Center for OCD, Anxiety & Related Disorders and one of six senior authors who supervised the research. “Over time, we’ve come to realize that OCD is not a disease of a single gene or specific brain region, but rather it’s a disease of circuits and hundreds of genes, which together contribute to the development of the disorder.”

Estimated to affect more than 3 million Americans, OCD causes unwanted, intrusive thoughts (obsessions) and urges to repeat specific behaviors (compulsions) — symptoms that can be debilitating. Current treatments include exposure therapy and response prevention (a form of cognitive behavioral therapy), medication or both.

In their study, investigators assessed relationships between gene expression, gene function and OCD, which long has been thought to be caused by a combination of genetics and environmental factors.

The new findings suggest OCD is more complex than conditions or characteristics influenced by single genes, such as Huntington’s disease or cystic fibrosis. Instead, it is closer to traits that are influenced by hundreds or thousands of genes, like height, blood pressure or depression.

“We identified 30 regions of the genome and 25 genes within those regions that are likely causal for OCD,” said Mathews, a McKnight Brain Institute investigator. “Expression of these genes are associated with specific brain regions and types of neurons — in particular, regions involved in decision-making, memory and higher-level cognitive functions.”

These findings are important, she said, because with no cure for OCD, understanding the patterns of gene expression in specific brain regions could help scientists eventually develop new drugs or improve current therapies like transcranial magnetic stimulation, a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain.

In addition, the study found OCD to be genetically related to other psychiatric disorders, including Tourette syndrome, anorexia, anxiety and depression.

“This study will help us to better understand the biological underpinnings of OCD and its relationships to other psychiatric illnesses, which often co-occur with OCD,” Mathews said.

The plethora of data is the result of a collaboration started more than 20 years ago, when the International OCD Foundation began building a network of researchers from various disciplines, including psychiatrists, geneticists, statisticians and more.

For the study just published, DNA samples and diagnosis data came from consenting individuals whose information was de-identified, meaning any personal details were removed. More than 18,000 cases came from health care professionals, health records or biobanks, while 30,000-plus came from 23andMe, the genetic testing and information company.

Next steps may include expanding the research to reveal other genes associated with OCD risk and to explore the genetic relationships between OCD and other disorders.

Ultimately, genetic studies such as this one may be useful in scouring newly available drug databases for possible ways to “repurpose” existing drugs formulated for similar targets.