The most striking feature of psychiatric disorders is the lack of specificity of the genetic risk factors

27 May, 2020

Shahar Shohat, Alana Amelan and Sagiv Shifman review and analyze the functional convergence of genetic risk factors for major neuropsychiatric disorders on molecular pathways, cell types and brain regions during developmental periods.

"We recently have been tremendously successful in identifying risk genes for psychiatric disorders by applying new technologies and through extensive collaboration between many scientists. In a way, too successful. The prodigious number of candidate risk genes and the genetic overlap between disorders makes the next step of studying the mechanisms challenging. Newly established detailed gene expression databases, covering brain cell types and different developmental stages, together with systems biology approaches, have been used to explore the convergence between genes and divergence between disorders. The results showed that across disorders, risk genes are likely to be intolerant to mutations and preferentially expressed in the brain. The disorders diverge mainly on the relative contribution of rare vs. common variants, and the timing of expression of the risk genes. Thus, the functional enrichment results are still crude and far from illuminating the neurobiological mechanisms for psychiatric disorders. Perhaps the convergence and divergence will only be found at the neural circuit level." 

Read the paper published in Biological Psychiatry