Obsessive-compulsive disorder has many unknowns, including what causes the symptoms, why symptoms vary widely between people, medications and treatments actually work, and why treatments work for some people rather than others. In our newly published study, my colleagues and I took a step forward by elucidating the genetics of OCD.

Obsessive-compulsive disorder is one of the most damaged diseases in the world. OCD affects approximately 50 people worldwide, one of the top ten reasons for loss of disability, resulting in harmful effects on a person’s ability to work and operate in the world and in the family.

People with this disease die prematurely from natural causes (such as infection or other diseases) and have a 300% higher chance of early death due to unnatural causes (such as accidents or suicides) than those without obsessive-compulsive disorder.

People with obsessive-compulsive disorder experience obsessions – disturbing, repetitive and unnecessary thoughts, fears or psychological images – as well as obsessiveness, such as repetitive behaviors and rituals to alleviate anxiety that is usually caused by obsession. For example, even if they know it is too much or illogical, they may wash their hands multiple times or in a specific way to eliminate bacteria. It is also common to avoid certain places or situations to relieve anxiety or prevent triggering obsession and compulsion.

Although the exact cause of OCD is not clear, researchers know that both genetic and environmental factors play a role in its development. Obsessive-compulsive disorder can run in the home; studies attribute 40% to 65% of OCD cases to genetic factors. Obsessive-compulsive disorder starting in childhood has a stronger genetic effect than obsessive-compulsive disorder starting in adulthood.

However, unlike some genetic diseases caused by a single defective gene, such as cystic fibrosis or Huntington's disease, OCD is affected by hundreds to thousands of genes that play a small part of the risk of the disease.

My colleagues and I analyzed the DNA of more than 53,000 people with obsessive-compulsive disorder and more than 2 million people without obsessive-compulsive disorder, which is the largest study of this condition. We have found hundreds of genetic markers that may be associated with OCD – we hope that the data will eventually lead to improved methods to identify people at risk for obsessive-compulsive disorder and online for better treatment.

How scientists study genetics of obsessive-compulsive disorder

To find genes involved in the risk of obsessive-compulsive disorder, the researchers used a method called genome-wide association study or GWAS. These studies compared dozens of DNA with hundreds of thousands of people with disease-free DNA, looking for slight differences in genetic material. These genetic markers may be associated with obsessive-compulsive disorder and may also indicate the presence of other genes associated with the disease.

In GWAS, scientists carefully tested each of the millions of genetic markers throughout the genome to identify people who were found more frequently in obsessive-compulsive disorder patients than in people without OCD. They then determined which genes these markers were associated with, their location in the body and how they contribute to the condition.

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We identified 30 regions in the genome associated with OCD, including 249 genes of interest. Among them, 25 genes cause the possibility of the development of obsessive-compulsive disorder.

The first three genes we found are also associated with other brain disorders such as depression, epilepsy, and schizophrenia. Several other genes of interest in OCD have also found genomic regions that play a role in adaptive immunity and are associated with other mental illnesses.

Importantly, no gene can predict or cause OCD on its own. Previous genetic studies have shown that all 23 pairs of chromosome genes may lead to the risk of obsessive-compulsive disorder.

Genetic insights into obsessive-compulsive disorder

Since each genetic marker or gene contributes very little to disease susceptibility, GWAS is of no use for identifying genes that cause OCD in a given person. Instead, this research helps scientists understand how the brain of people with obsessive-compulsive disorder works and whether obsessive-compulsive disorder shares its genetic roots with the conditions that usually occur.

For example, we found that genetic markers associated with OCD are highly active in several brain regions known to play a role in the development of the disease. These brain regions are collectively involved in planning, decision making, motivation, error detection, emotional regulation, and fear and anxiety, all of which can malfunction in obsessive-compulsive disorder.

We also found associations with a brain region called the hypothalamus that translates emotions such as fear, anger, anxiety, or excitement into physical reactions. The hypothalamus has not been directly associated with OCD before, but it is part of a network of brain regions that may cause its symptoms.

Furthermore, we found that certain types of brain cells, especially mespinal neurons in brain regions called striatum - were closely related to the OCD genes we identified. Meso-spinal neurons play an important role in habit formation, i.e. the process in which behavior becomes automatic and habitual - considering compulsion. Specific receptors on mespit neurons are common targets for drugs sometimes used to treat obsessive-compulsive disorder.

Our results can help researchers better understand the relationship between obsessive-compulsive disorder and other diseases. We found genetic links between obsessive-compulsive disorder and several other mental illnesses, especially anxiety, depression, anorexia and Tourette syndrome. Obsessive-compulsive disorder patients also exhibit lower genetic risks, such as alcohol dependence and risk-taking behaviors, consistent with what doctors see in clinics: Many people with obsessive-compulsive disorder tend to be cautious and avoid risks.

Surprisingly, we also found genetic overlap between conditions associated with OCD immunity. Although OCD appears to be associated with an increased risk of asthma and migraine, it may also be associated with a lower risk of inflammatory bowel disease. These findings may lead to new insights on the role of immune system and inflammation in brain health.

More effective treatment for obsessive-compulsive disorder

Obsessive-compulsive disorder is a complex disease that may look very different from people. Understanding the genetic and biological factors behind obsessive-compulsive disorder helps researchers get closer to better diagnosis, treatment, and even prevention.

As a practicing psychiatrist and researcher, I have spent my career understanding the causes of obsessive-compulsive disorder and improving the lives of people with this disease. Through larger research and ongoing research, my team and I hope to better match specific biological patterns with individual symptoms.

Over time, this may lead to more personalized and effective treatments – improving the lives of millions of people with obsessive-compulsive disorder around the world.