Researchers identify specific genes that cause schizophrenia

A substantial number of individual genes that potentially play essential roles in schizophrenia have been uncovered in the largest-ever genomic analysis of the psychiatric condition.

Researchers identify specific genes that cause schizophrenia

Image Credit: Cardiff University

To better comprehend the genes and molecular processes that drive schizophrenia, a collaboration of hundreds of researchers from 45 nations studied DNA from 76,755 people with the disease and 243,649 people who did not.

The Psychiatric Genomics Consortium study, conducted by Cardiff University researchers, discovered more genetic ties to schizophrenia than ever before in 287 distinct areas of the genome, the human body’s DNA blueprint.

They also discovered that genes associated with schizophrenia are concentrated in brain cells known as neurons, but not in any other tissue or cell type, implying that the biological role of these cells is critical in schizophrenia.

This global study, according to the researchers, gives the most light yet on the genetic foundation of schizophrenia. It was just published in the prestigious international journal Nature.

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.”

Michael O’Donovan, Study Co-Lead Author and Professor, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University

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,” O’Donovan added.

According to the World Health Organization, schizophrenia is a severe psychiatric condition that begins in late adolescence or early adulthood and affects one in every 300 persons worldwide at any given moment.

The researchers discovered a “significant rise” in the number of genomic areas linked to schizophrenia in the largest genome-wide association analysis to date. They then utilized advanced systems to determine 120 genes that are likely to contribute to the illness within these regions.

In addition to being the largest study of its kind, the scientists included over 7,000 participants of African American or Latino background in what they describe as a tiny step toward ensuring that genetic breakthroughs benefit those who are not of European ancestry.

Despite the fact that there are many genetic variants linked to schizophrenia, the study found that they are concentrated in genes expressed in neurons, indicating that neurons are the most relevant source of illness. The results also suggest that aberrant cell function in schizophrenia affects several brain areas, which could explain the disorder’s wide range of symptoms, which include hallucinations, delusions, and difficulty thinking rationally.

Coordinating their research with a parallel study comprising many of the same experts, including those from Cardiff University, and directed by the Broad Institute of Harvard and MIT, and published in Nature in parallel, improved the team’s capacity to link to specific genes and regions of biology.

The research examined mutations that, while rare, have significant consequences for the small percentage of people who carry them and discovered overlapping genes and biological characteristics.

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, says, “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,” Walters added.

The National Institute of Mental Health (NIMH) in the United States funded the Psychiatric Genomics Consortium, and the Medical Research Council-funded the work in Cardiff.

These results, achieved through a global collaboration unprecedented in scope, mark an important step forward in our understanding of the origins 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.”

Dr Joshua Gordon, Director, National Institute of Mental Health

The usefulness and power of big samples in genetic studies to get insights into psychiatric diseases have been established in this work. To expand the understanding of schizophrenia, the team is currently looking for more research participants and building larger, more diverse datasets.

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