New insights and perspectives on the genetics of obsessive-compulsive disorder

Abstract

Psychiatric genetic research has exploded in search of polygenic risk factors over the past decade, but because of the complexity and heterogeneity of mental illnesses, using the current understanding of the genome has not reached the conclusion of finding a cause for psychiatric disorders. Obsessive-compulsive disorder is a relatively common and often debilitating neuropsychiatric disorder that has not been the primary focus in psychiatric research. Clinicians and researchers who have dedicated to investigate the genetics of obsessive-compulsive disorder have detected a strong genetic involvement. This review will provide an update and a new perspective on the current understanding of the genetics of obsessivecompulsive disorder, which includes epidemiological data, family and twins studies, candidate gene studies, genomewide association studies, copy-number variants, imaging genetics, epigenetics, and gene-environment interaction.

Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls

“…Our study expands the literature on orbitofronto-striatal dysfunctioning that has previously described in terms of increased activity and connectivity of the OFC in the OCD phenotype 51 – 53 by providing evidence for an association with the genetic risk for OCD. While previous genetic studies have reported effects of gene variants on OFC morphometry 20 , 21 , the current study showed that genetic risk for OCD may affect OFC functioning during a cognitively demanding task (n-back).…”

“…Previous morphometric imaging genetics studies have identified several core regions that were associated with candidate genes related to the serotonergic, dopaminergic, and glutamatergic systems (for review see 20 , 21 ). Gene variants of the serotonergic and glutamatergic system affected grey matter volume in orbitofrontal cortex (OFC).…”

Genetics of obsessive-compulsive disorder

“…Furthermore, future studies should examine the role of environmental factors in terms of gene × environment interactions, other structural variants such as variable number of tandem repeats (VNTRs) in large-scale sequencing studies (Trost et al, 2020 ) and epigenetic mechanisms, such as DNA methylation and mRNA expression. Understanding the underlying biological mechanisms of OCD will hopefully lead to the introduction of new treatment strategies and individually tailored interventions (Zai et al, 2019 ). Exploring associations between genetics and psychological treatment outcome will also contribute to the development of personalized medicine in OCD (Lester & Eley, 2013 ).…”

A dimensional perspective on the genetics of obsessive-compulsive disorder

“…Here we review genetic evidence obtained using approaches that employ both a diagnostic (case/control) and a dimensional (continuous phenotype) framework and discuss the implications for future genetic research of OCD. We only briefly address the genetic findings from studies using the diagnostic conceptual framework in OCD, as recent reviews have discussed these in depth [26][27][28][29]. The majority of this review focuses instead on recent advances in OCD genomics research by examining the evidence for genetic correlates of OCD using a dimensional perspective.…”