First genome-wide de-novo mutational analysis of a family with obsessive-compulsive disorder

Previous GWAS studies have shown a link between the heritability of OCD and de novo mutations (de-novo mutations), or genetic changes that first appear as a result of mutations in parental germ cells

Obsessive-compulsive disorder (OCD) is a mental illness that affects one percent of the U.

Obsessive-compulsive disorder is characterized by chronic anxiety, depression, obsessive-compulsive behavior, and a difficult quality of life, and understanding OCD is important to help treat individuals with the disorder

Recent research suggests that genetic variants may constitute risk factors for the development of OCD

Previous GWAS have suggested a link between OCD heritability and de novo mutations, or genetic changes that first appear due to mutations in parental germ cells (sperm or egg)

By sequencing the genomic DNA of 53 unrelated parent-child families, the researchers found that a subset of de novo mutations related to the regulation of chromatin modifications play an important role in OCD risk factors

In the new article, the researchers note that emerging mutations in three chromatin modifiers -- SETD5, KDM3Band ASXL3 -- suggest "OCD candidate risk genes" because of their ability to regulate neurotransmitter expression through epigenetic modification .

"We found significant changes in overall expression between KDM3B and the dopamine gene between

De novo structural variation

Furthermore, de novo structural variants within the genomes of OCD-affected individuals suggest a heterozygous de novo deletion of the FBLgene , resulting in the OCD phenotype .

According to the researchers, these rare de novo mutations "are significantly enriched in promoter-anchored chromatin loops .

Genome sequencing of these OCD trio allowed the researchers to compare de novo mutational patterns in OCD-affected individuals with tardive dyskinesia (TD), which showed some similarities

However, studies have shown that genes carrying these mutations are differentially expressed in the brain: OCD mutant genes are enriched in dorsal thalamus and astrocytes, while TD mutant genes are enriched in occipital cortex and GABAergic neurons

"These results suggest that chromatin modifications involving SETD5, KDM3B, ASXL3 and FBLmay be upstream regulators of expression of the neurotransmitter system that controls essential neurocognitive functions .