Through whole exome sequencing, researchers have identified ten new genes involved in the development of schizophrenia. This finding may aid the development of future therapeutics.
Schizophrenia is a severe psychiatric disorder with a known underlying genetic risk factor. Although previous genome-wide association studies have discovered hundreds of common risk loci, very few have resulted in validated function variants that actually explain the disease pathogenesis.
Now, researchers have been able to gain a much deeper insight into the genetic underpinnings of schizophrenia. Through whole exome sequencing, the team have implicated ten new genes involved in schizophrenia development.
“The main aim of our research is to understand the genetic causes of schizophrenia and motivate the development of new therapeutics,” explained project lead Tarjinder Singh who is affiliated with both Massachusetts General Hospital and Harvard Medical School (both MA, USA).
“Drug development for schizophrenia has had limited progress in the last 50 years, but in the last decade, we have started to make genetic discoveries that help us better understand the mechanisms underlying the disorder.”
Previous attempts have been limited since the changes associated with schizophrenia development are rare in the population. As such, very large sample sizes are required to allow them to be studied with enough statistical power to draw definitive conclusions.
- Unsheathing schizophrenia
- The epigenetics of neuropsychiatric disorders
- Schizophrenia’s effect on synaptic function
This research, presented recently at the American Society of Human Genetics 2019 Annual Meeting in Houston (TX, USA), analyzed data from 25,000 people with schizophrenia and 100,000 people without from five different continental populations.
The huge scale of the sample allowed the researchers to, for the first time, identify ultra-rare variants in ten genes that contributed to substantial risk for schizophrenia. Two of these genes, GRIN2A and GRIA3, coded for glutamate receptors, a type of protein known to be involved in brain cell communication.
The researchers believe that it is decreased function of these receptors that causes the common symptoms associated with schizophrenia. This finding could aid in developing effective therapeutics for schizophrenia by providing a suitable target.
The researchers also identified a significant overlap with risk genes for severe neurodevelopmental delay and autism. By comparing these conditions, researchers aim to identify the specificity of the identified genes and uncover any wider biological effects.
“Overall, this method is a powerful way to look at complex traits, and combining results from genome-wide association studies and exome sequencing will teach us a lot about the biology underlying human diseases,” remarks Singh. “Now that we know how to do it, the biological work is what comes next.”
Written ByKatie Gordon
SourceSingh T, Neale BM, Daly MJ. PgmNr 3: Exome sequencing of 25,000 schizophrenia cases and 100,000 controls implicates 10 risk genes, and provides insight into shared and distinct genetic risk and biology with other neurodevelopmental disorders. Presented at: American Society of Human Genetics 2019 Annual Meeting. Houston, TX, USA, 15 – 19 October 2019.https://eventpilotadmin.com/web/page.php?page=IntHtml&project=ASHG19&id=1922937The American Society of Human Genetics. Researchers glean new insights into biological underpinnings of schizophrenia. Press release: https://www.ashg.org/