(Vienna, 12 April 2022) In the largest study so far conducted into schizophrenia, which included more than 320,000 participants, scientists from the Psychiatric Genomics Consortium (PGC), a group of several hundred researchers from 45 countries, identified a large number of genes that may play a significant role in the disorder. Researchers from MedUni Vienna were also involved in the study, which was recently published in the highly regarded journal "Nature".
"Although previous analyses have identified associations between schizophrenia and many DNA variations, these could only be assigned to specific genes in isolated cases," commented co-author and member of the PGC since its early years, Dan Rujescu, head of the Division of General Psychiatry at the Medical University of Vienna's Department of Psychiatry and Psychotherapy.
"The recent study, which was only possible through international collaboration between researchers on an unprecedented scale, not only increased the number of these associations significantly but also enabled us to link many of them to specific genes."
Schizophrenia is a serious psychiatric disorder that begins in late adolescence or early adulthood and affects about one in 300 people worldwide, according to the World Health Organization.
120 specific genes identified
Data analysis of 76,755 individuals with and 243,649 without the disorder revealed associations with schizophrenia in 287 distinct genomic loci , a far greater number of genetic associations than ever before. Using advanced methods, it was then possible to identify 120 specific genes that are likely to contribute to the disorder.
Interestingly, the genetic risk for schizophrenia was found to be particularly high in those genes that contain blueprints for proteins concentrated in the brain's neurons, suggesting that these cells are the primary site of pathology.
The findings also suggest that abnormal neuronal function in schizophrenia affects multiple regions of the brain, which may explain the wide range of symptoms, including hallucinations, delusions, and problems with thinking clearly.
Not only is it the largest study of its kind but the researchers included more than 7,000 people of African American or Latino descent in the study, which they say is a small step toward ensuring that advances from genetic studies do not only benefit people of European descent.
According to the research team, this global study sheds the clearest light yet on the genetic basis of schizophrenia. Rujescu adds: "I am very pleased to see how the initial genome-wide association studies of 2008 and 2009, in which my research group played a key role, have now become so comprehensive and so successful."
Accompanying study investigated gene mutations
The team's ability to make establish a link to specific genes and areas of biology was enhanced by coordinating their work with a companion study involving many of the same scientists led by the Broad Institute of MIT and Harvard and published in parallel in "Nature".
This further study examined mutations that are exceedingly rare but have major impacts on the small percentage of people who carry them and found overlapping genes and overlapping biological aspects.
This represents a further crucial step towards clarifying the causes of this complex disorder. However, there is still plenty of work to be done across disciplines before the growing body of genetic knowledge can be integrated into a detailed understanding of disease mechanisms and thus used to develop new treatment strategies, Rujescu said.
The Psychiatric Genomics Consortium is funded by the US National Institute of Mental Health (NIMH).
Trubetskoy, V., Pardiñas, A.F., Qi, T. et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature (2022). https://doi.org/10.1038/s41586-022-04434-5 Nature. 2022 Apr 8. doi: 10.1038/s41586-022-04434-5. Epub ahead of print. PMID: 35396580.