There has been a spectacular breakthrough in schizophrenia research. In the largest study of its kind, Dutch and international researchers, including VU professor Danielle Posthuma, have discovered six new schizophrenia genes.
The international collaboration, known as the Psychiatric Genomics Consortium, published its results in Nature Genetics on 21 November. The results confirm the important role of genes in the development of schizophrenia and provide new leads for early diagnosis.
The study is based on information gathered from more than 40,000 people and was carried out by more than 170 scientists and clinicians in Northern America and Europe. The team developed a standardised method for analysing the DNA of people with schizophrenia and healthy control subjects on the Dutch LISA supercomputer using so-called ‘microarrays’ (technology which uses a microchip to determine whether certain pieces of DNA are missing or duplicated).
1% have schizophrenia
Schizophrenia occurs in around one in a hundred people and is a serious psychiatric disorder affecting how a person thinks, feels and behaves. The condition is usually diagnosed in the late teens or early adulthood, and takes a chronic course. Previous studies of duplications and deletions in DNA had already suggested that these rare genetic variants play an important role in the etiology of schizophrenia. However, these studies were based on small samples which meant that it was never possible to establish a robust link between genomic duplications or deletions and schizophrenia.
In this new study, researchers found that people with schizophrenia had more of these duplications and deletions in their DNA on average than people without schizophrenia. In the places where these duplications and deletions occur, there are several genes that are particularly involved in the operation of the contact points between nerve cells.
Unprecedented sample size
‘This study is an important step forward in understanding the genetics of schizophrenia. Due to its unprecedented sample size (around 21,000 schizophrenia patients and around 20,000 controls), we were able to detect several new risk genes,’ said Danielle Posthuma, professor in Complex Trait Genetics at the VU, and one of the principal investigators. ‘The majority of these genes play an important role in synaptic processes in the brain. Understanding the underlying biological processes in schizophrenia gives fresh leads for developing new therapies for this serious condition.’
As with many other psychological conditions, you can’t just carry out an x-ray or take a simple blood test to diagnose schizophrenia. With this research, clinicians can now establish through the DNA whether someone is a carrier of rare risk variants for schizophrenia. The researchers hope that the newly developed analysis method will also produce new findings for other conditions.
800 researchers from 38 countries
The research was carried out under the auspices of the Psychiatric Genomics Consortium (PGC), which was established in 2007 and consists of more than 800 researchers from 38 countries. The PGC is the largest consortium and also the largest biological experiment in the history of psychiatry.
The consortium’s central analyses have been carried out since 2007 on the Dutch Genetic Cluster Computer, which is part of the LISA cluster hosted by SURFSara. The Psychiatric Genomics Consortium is largely funded by the American National Institute of Mental Health. The Vrije Universiteit and NWO (the Dutch Organisation for Scientific Research) fund the Genetic Cluster Computer.