De novo mutations identified by whole-genome sequencing implicate chromatin modifications in obsessive-compulsive disorder.
Sci Adv
; 8(2): eabi6180, 2022 01 14.
Article
in En
| MEDLINE
| ID: mdl-35020433
ABSTRACT
Obsessive-compulsive disorder (OCD) is a chronic anxiety disorder with a substantial genetic basis and a broadly undiscovered etiology. Recent studies of de novo mutation (DNM) exome-sequencing studies for OCD have reinforced the hypothesis that rare variation contributes to the risk. We performed, to our knowledge, the first whole-genome sequencing on 53 parent-offspring families with offspring affected with OCD to investigate all rare de novo variants and insertions/deletions. We observed higher mutation rates in promoter-anchored chromatin loops (empirical P = 0.0015) and regions with high frequencies of histone marks (empirical P = 0.0001). Mutations affecting coding regions were significantly enriched within coexpression modules of genes involved in chromatin modification during human brain development. Four genesSETD5, KDM3B, ASXL3, and FBLhad strong aggregated evidence and functionally converged on transcription's epigenetic regulation, suggesting an important OCD risk mechanism. Our data characterized different genome-wide DNMs and highlighted the contribution of chromatin modification in the etiology of OCD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Epigenesis, Genetic
/
Obsessive-Compulsive Disorder
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Sci Adv
Year:
2022
Document type:
Article
Affiliation country:
China