An international team with Spanish participation has shed light on the genetic roots of obsessive-compulsive disorder (OCD), a problem estimated to affect one in every 100 people and characterized by unwanted repetitive thoughts and compulsive behaviors.
For the first time, the study has identified 30 regions in the DNA associated with a higher risk of developing OCD, a disorder with a clear genetic basis but also influenced by environmental factors.
Previously, the genetic variants associated with the disorder were not well understood, a question addressed by a collaboration of over 200 specialists worldwide, including scientists from the Genomic Medicine Group of the University of Santiago de Compostela (USC), the Singular Center for Research in Molecular Medicine and Chronic Diseases of the USC (CiMUS), and the Galician Public Foundation of Genomic Medicine. The findings gathered after over 20 years of work have been published in the journal Nature Genetics.
The study conducted a genome-wide analysis (GWAS) of 53,660 cases of OCD and over 2 million controls, the largest study of its kind to date on this disorder.
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In the 30 identified regions in the DNA related to the disorder, located in different genome locations and associated with different brain circuits, scientists found 249 associated genes, of which 25 candidate genes showed a strong association with the disorder.
"Not all identified variants confer a similar risk for obsessive-compulsive disorder (OCD); some contribute more to the risk than others," explains Cristina Rodríguez Fontenla, a researcher at CiMUS and one of the scientists with a prominent role in analyzing the data of this study coordinated from Dalhousie University (Canada).
Among the 25 genes most related to the disorder, some stand out "such as CTNND1, WDR6, and DALRD3. These analyses include not only genetic data but also expression data, allowing the identification and prioritization of genes with potential functional effects," adds the specialist.
Nevertheless, Rodríguez Fontenla points out that "the accumulation of multiple risk variants does not guarantee the development of OCD" due to the variable gene expression and the role of environmental factors in the disorder's development.
Researchers Teresa Rodríguez Fontenla and Ángel Carracedo.CiMUS
The study also found that OCD is genetically related to other psychiatric disorders such as Tourette syndrome, anorexia nervosa, anxiety, and depression.
In Spain, it is estimated that around 400,000 people suffer from OCD. The most common issues related to obsessive behaviors or compulsions are related to the need for order and symmetry, doubts and insecurity, or fear of contamination or dirtiness.
Treatment often involves a combination of psychotherapeutic treatment with medications such as selective serotonin reuptake inhibitors.
For the researchers involved in this study, which also involved Ángel Carracedo, a professor at the University of Santiago de Compostela, "understanding gene expression patterns in specific brain regions could eventually help scientists develop new drugs or improve current therapies such as transcranial magnetic stimulation, a non-invasive procedure that uses magnetic fields to stimulate brain nerve cells," they stated in a press release.
One limitation of the study, as acknowledged by Rodríguez Fontenla, is that "all samples used come from individuals of European descent. This means that these associations are specific to European populations, and it cannot be assumed that these same genome regions confer a similar risk in individuals of other ancestries."
In this regard, the researcher highlights the "need to include samples of diverse genetic ancestry, which can help identify new risk genes and better understand the genetic architecture of OCD in different population groups," she indicates.
"There is an effort by consortia such as the Psychiatric Genomics Consortium that bring together research groups worldwide to gather large cohorts of patients and controls and enhance scientific collaboration to continue advancing in this field," she adds.