Convergence and Divergence in the Genetics of Psychiatric Disorders From Pathways to Developmental Stages

Shahar Shohat, Alana Amelan, Sagiv Shifman*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations

Abstract

In the past decade, the identification of susceptibility genes for psychiatric disorders has become routine, but understanding the biology underlying these discoveries has proven extremely difficult. The large number of potential risk genes and the genetic overlap between disorders are major obstacles for studying the etiology of these conditions. Systems biology approaches relying on gene ontologies, gene coexpression, and protein-protein interactions are used to identify convergence of the genes in relation to biological processes, cell types, brain areas, and developmental stages. Across psychiatric disorders, there is a clear enrichment for genes expressed in the brain and especially in the cortex, but a higher resolution is vastly dependent on sample size and statistical power. There is indication that susceptibility genes tend to be expressed in the brain during periods preceding the typical onset of the disorders. Thus, the role of genes in prenatal brain development is more pronounced for childhood-onset disorders, such as autism spectrum disorder and attention-deficit/hyperactivity disorder, but is much less so for bipolar disorder and depression. One of the most consistent findings across multiple disorders and classes of genetic variants is the role of genes intolerant to mutations in psychiatric disorders, yet this association is more pronounced for disorders with a clear neurodevelopmental component. Notwithstanding, a detailed understanding of the neurobiology of psychiatric disorders is still lacking. It is possible that it will only be revealed by studying the risk genes at the level of the development and function of neuronal networks and circuits.

Original languageAmerican English
Pages (from-to)32-40
Number of pages9
JournalBiological Psychiatry
Volume89
Issue number1
DOIs
StatePublished - 1 Jan 2021

Bibliographical note

Publisher Copyright:
© 2020 Society of Biological Psychiatry

Keywords

  • Convergence
  • Exome sequencing
  • Functional genomics
  • Genes intolerant to mutations
  • Genome-wide association studies
  • Psychiatric disorders
  • Rare variants
  • Systems biology

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