Obsessive-Compulsive Disorder (OCD) may Hold Varied Genetic Mutations

Distinct patterns of genetic mutations are linked with obsessive-compulsive disorder (OCD) in humans.

Distinct patterns of genetic mutations are linked with obsessive-compulsive disorder (OCD) in humans – the gene discovery that may hold key to better therapies for OCD, as per a study at the Columbia University Vagelos College of Physicians and Surgeons and several other institutions, published online in Nature Neuroscience.

Obsessive-compulsive disorder (OCD) is a disabling mental disorder characterized by repeated thoughts ("obsessions") or urge to perform certain practices repeatedly ("compulsions") that it greatly impairs daily lives and produces distress.

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Obsessive compulsive disorder (OCD) is an anxiety disorder characterized by anxious unwanted thoughts or behavior, which the patient is unable to control.

‘Distinct patterns of genetic mutations are found to be linked with obsessive-compulsive disorder (OCD) in humans. These present gene findings thereby hold a promising approach to precision medicine for OCD, that would ultimately transform its diagnostic and treatment strategies in the future.’

OCD is twice as common as schizophrenia and often runs in families. It affects 1% to 2% of the population. Despite the fact that many OCD genes remain unknown (mainly due to statistically unreliable evidence), they play a larger role in determining the development of the disease in individuals.

Burden of Genetic Mutations in OCD

"Many neurological diseases are influenced by strongly acting mutations which can cause disease by themselves. These mutations are individually very rare but important to find because they can provide a starting point for the development of therapeutics that target precise underlying causes of disease," says David Goldstein, Ph.D., director of the Institute for Genomic Medicine at Columbia and a senior author on the new paper.

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Several studies over the past years have mainly focussed on the "candidate gene" approach where only plausible genes that are involved in pathogenesis are explored for genetic signatures of risk. However, genome-wide analyses study all the genes in the genome at the same time and this can securely implicate genes in disease risk.

The study team thereby utilized a genome-wide approach with high-throughput sequencing and computational biology techniques to identify relevant genes in more than 1,300 OCD patients. This was compared to similarly large control groups.

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Out of the Box Approach to OCD

It was shown that a strong correlation exists between OCD and rare mutations, particularly in a gene called SLITRK5 that had been previously linked to OCD in candidate-gene studies.

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This may encourage pharmaceutical companies and translational researchers to develop drugs that target this gene. A specific pattern of variation in other genes were also identified by the study team.

"When you look at genes that do not tolerate variation in the human population, those are the genes most likely to cause disease, and with OCD, we see an overall increased burden of damaging mutations in those genes compared to controls. That's telling us that there are more OCD genes to be found and where to find them," says Goldstein.

Conventional treatments of OCD are effective in only about half of patients. Hence the present findings hold a promising approach to precision medicine for OCD that would ultimately transform its diagnostic and treatment strategies.

Source-Medindia