Researchers may have discovered a potential cause of schizophrenia, identifying particular genes that may be instrumental in developing the psychiatric disorder.
In the most extensive genetic investigation to date, the Psychiatric Genomics Consortium study, which comprises a group of 100 researchers from 45 countries, examined DNA from 76,755 people with schizophrenia and 243,649 without it. The analysis revealed a plethora of genes in 287 different regions of the genome that could be a cause of schizophrenia. The study included 7,000 people with either African American or Latino ancestries in an effort to advance genetic studies to benefit people beyond those of European origins.
Moreover, the investigation signified the genetic risk for schizophrenia is seen in genes concentrated in the brain’s cells called neurons; however, it is not present in any other tissue or cell type, meaning the biological role of these cells may be a crucial cause of the disorder.
Professor Michael O’Donovan, the co-author of the research from the Division of Psychological Medicine and Clinical Neurosciences at Cardiff University, commented: “Previous research has shown associations between schizophrenia and many anonymous DNA sequences, but rarely has it been possible to link the findings to specific genes.
“The present study not only vastly increased the number of those associations, but we have now been able to link many of them to specific genes, a necessary step in what remains a difficult journey towards understanding the causes of this disorder and identifying new treatments.”
The findings of the study are published in Nature.
Uncovering the cause of schizophrenia
Schizophrenia is a severe psychiatric condition that usually arises in late adolescence or early adulthood, which, according to the World Health Organization (WHO), affects around one in 300 people globally.
In this novel investigation, the researchers discovered a significant increase in the number of genomic regions associated with the disorder, finding 120 genes that are a likely cause of schizophrenia.
Despite a large number of genetic variants being crucial in the development of schizophrenia, the analysis showed they are concentrated in genes expressed in neurons, meaning these cells may be the most important site of pathology. Moreover, the results suggest that abnormal neuron function in schizophrenia impacts a range of brain areas, potentially explaining the condition’s diverse symptoms, which include hallucinations, delusions, and issues with thinking clearly.
Enhancing psychiatric disorder research
The researchers’ ability to associate certain genes and brain regions was made possible to do collaborating their investigation with a companion study involving many of the same scientists, including those from Cardiff University and the Broad Institute of Harvard and MIT. This investigation examined rare mutations that can significantly affect people who carry them, identifying overlapping genes and aspects of biology.
Professor James Walters, co-lead author on the Cardiff-led paper and Director of the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University, said: “Whilst people with schizophrenia can recover, many do not respond well to treatments, experience long-term problems with their mental and physical health, as well as impacts on relationships, education, and work.
“We hope the findings in this, and the companion studies, can be used to advance our understanding of the disorder and facilitate the development of radically new treatments. However, those processes are often not straightforward, and a lot of work by other neuroscientists is needed to translate the genetic findings into a detailed understanding of disease mechanisms.”
Dr Joshua Gordon, Director of the National Institute of Mental Health (NIMH), which funded the study, said: “These results, achieved through a global collaboration unprecedented in scope, mark an important step forward in our understanding of the cause of schizophrenia. The findings will allow researchers to focus on specific brain pathways in the ongoing hunt for novel therapies for this serious mental illness.”
The team is now aiming to recruit more research participants to create more extensive and diverse datasets to build on our knowledge of schizophrenia.