Largest international study of its kind finds new schizophrenia risk genes

Results of the International Psychiatric Genomics Consortium unveiled

TORONTO – Canadian and international scientists have uncovered six new schizophrenia risk genes in the largest study of its kind. The results of the international Psychiatric Genomics Consortium CNV working group are published in the Nov. 21 advance online edition of Nature Genetics, and further support the important role genes play in susceptibility to schizophrenia, and may be helpful in early diagnosis.

The study included over 40,000 people and more than 170 scientists and clinicians from across North America and Europe. The team built a standardized pipeline to analyze the genes of individuals with schizophrenia and as well as healthy controls using microarrays (technology which uses a microchip to determine if a genome has either missing or duplicated pieces of DNA).  

Schizophrenia is diagnosed in one in 100 people and is a chronic and severe psychiatric condition that affects how a person thinks, feels and behaves with onset in late teens or early adulthood. Previous studies of genomic copy number variation (CNV), which are duplications and deletions in the genes, have established an important role for rare genetic variants in the etiology of schizophrenia, but many studies are underpowered to robustly confirm these genetic associations.

In this study, the researchers reported that individuals with schizophrenia tended to carry more genetic alterations than those in the control group, and these rare CNVs tended to affect genes in the synapse (the junction between two nerve cells).

“This study represents a milestone. Because of the systematic analysis in a large number of individuals with schizophrenia we were able to implicate several new genes, many of which are in the same biological pathways found in the brain,” says Dr. Christian Marshall, Associate Director in Genome Diagnostics and The Centre for Applied Genomics at The Hospital for Sick Children (SickKids), and first author of the paper. “Making the connection between these common pathways can lead to development of targeted therapies for schizophrenia and other psychiatric conditions.”

According to Marshall, like many mental illnesses you can’t just take an x-ray or simple blood test to confirm a diagnosis. With this research, clinicians have genetic tools to help find more definitive answers as to whether a patient carries the risk genes for schizophrenia. The hope is this standardized pipeline will also accelerate discoveries for other conditions.

The team was co-led by Dr. Stephen Scherer, Senior Scientist and Director of The Centre for Applied Genomics at SickKids and the McLaughlin Centre at the University of Toronto and Dr. Jonathan Sebat, Director of Beyster Center for Psychiatric Genomics and Professor in the Department of Psychiatry, University of California San Diego, School of Medicine.

The Psychiatric Genomics Consortium began in early 2007 includes over 800 investigators from 38 countries. The PGC is the largest consortium and the largest biological experiment in the history of psychiatry. Core funding for the Psychiatric Genomics Consortium is from the US National Institute of Mental Health.

This paper is an example of how SickKids is contributing to making Ontario Healthier, Wealthier and Smarter.