The team of Lin Guanning and Wang Zhen of Shanghai Jiaotong University first proposed that the pathogenesis of obsessive-compulsive disorder may be related to the disorder of chromatin structure

Obsessive-compulsive disorder (OCD) has a lifetime prevalence of up to 3% worldwide.

A growing body of research is beginning to demonstrate that ultra-rare but potentially high penetrance mutations may be an important factor in the pathogenesis of psychiatric disorders

The researchers firstly sequenced the whole genome of 53 nuclear families, obtained all the genetic variants carried by obsessive-compulsive disorder patients and their healthy parents, and screened out ultra-rare de novo mutations that only exist in patients.

When the researchers further used human brain expression data to construct a brain gene interaction network during embryonic and postnatal periods, they found that the genes in which the above mutations were located were concentrated in a biological sub-network with a "chromatin regulation" function, which was associated with many neural networks.

In addition, the study also found that about half of the patients carried at least one severe de novo mutation, providing new evidence for the previously unresolved "de novo mutation hypothesis" of obsessive-compulsive disorder

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In addition, by comparing OCD genes with tic genes, the researchers also found an interesting result: These are two psychiatric disorders with some similar clinical phenotypes, although their causative genes are highly similar.

The related paper "De novo mutations identified by whole-genome sequencing implicate chromatin modifications in obsessive-compulsive disorder" was published online by Science Advances on January 12