Scientists analysed DNA from more than 300,000 people with and without the psychiatric disorder
From: Cardiff
University
April 6, 2022 -- The largest ever genetic study of
schizophrenia has identified large numbers of specific genes that could play
important roles in the psychiatric disorder. A group of hundreds of researchers
across 45 countries analysed DNA from 76,755 people with schizophrenia and
243,649 without it to better understand the genes and biological processes
underpinning the condition. The new study found a much larger number of genetic
links to schizophrenia than ever before, in 287 different regions of the
genome, the human body's DNA blueprint.
Furthermore, they showed that genetic risk for
schizophrenia is seen in genes concentrated in brain cells called neurons, but
not in any other tissue or cell type, suggesting it is the biological role of
these cells that is crucial in schizophrenia.
The research team say this global study sheds the
strongest light yet on the genetic basis of schizophrenia. It is published
today in the 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," said co-lead author
Professor Michael O'Donovan, from the Division of Psychological Medicine and
Clinical Neurosciences at 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."
Schizophrenia is a serious psychiatric disorder that
starts in late adolescence or early adulthood and at any one time affects
around one in 300 people worldwide, according to the World Health Organization.
In the largest genome-wide association study to
date, the research team identified a "substantial increase" in the
number of genomic regions associated with schizophrenia. Within these regions,
they then used advanced methods to identify 120 genes likely to contribute to
the disorder.
As well as being the largest study of its kind, the
researchers included more than 7,000 people with either African American or
Latino ancestries in what they say is a small step towards making sure advances
that come from genetic studies can benefit people beyond those of European
ancestries.
Although there are large numbers of genetic variants
involved in schizophrenia, the study showed they are concentrated in genes
expressed in neurons, pointing to these cells as the most important site of
pathology. The findings also suggest abnormal neuron function in schizophrenia
affects many brain areas, which could explain its diverse symptoms, which can
include hallucinations, delusions and problems with thinking clearly.
The team's ability to link to specific genes and
areas of biology was enhanced by co-ordinating their work with a companion
study involving many of the same scientists, including those from Cardiff
University, led by the Broad Institute of Harvard and MIT, and published in
Nature in parallel.
That study looked at mutations that, while very
rare, have large effects on the small proportion of people that carry them, and
found overlapping genes and overlapping 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."
The Psychiatric Genomics Consortium is funded by the
National Institute of Mental Health (NIMH) of the USA and work in Cardiff was
additionally supported by the Medical Research Council.
Dr Joshua Gordon, Director of NIMH, said:
"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."
This study has demonstrated the importance and power
of large samples in genetic studies to gain insights into psychiatric
disorders. The team are now seeking to recruit more research participants and
build larger, more diverse datasets to further advance our understanding of
schizophrenia.
https://www.sciencedaily.com/releases/2022/04/220406132406.htm
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