Large numbers of specific genes could play important roles in the development of schizophrenia, the largest genetic study into the disorder has found.
The Psychiatric Genomics Consortium study, led by Cardiff University, involved hundreds of researchers across 45 countries and they found 287 different regions of the genome linked to schizophrenia.
They analysed DNA from 76,755 people with schizophrenia and 243,649 without the disorder and it included more than 7,000 people with either African American or Latino ancestries, in what the researchers say is a small step towards making sure genetic studies can benefit people beyond those of European ancestries.
They found that genetic risk for schizophrenia is seen in genes concentrated in neurons, but not in any other tissue or cell type.
This, say the researchers, suggests the biological role of these cells is crucial in schizophrenia. Their findings are published in the latest edition of 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.”
The team identified a “substantial increase” in the number of genomic regions associated with schizophrenia and within these regions, they used advanced methods to identify 120 genes likely to contribute to the disorder.
While there are large numbers of genetic variants involved in schizophrenia, the study showed they are concentrated in genes expressed in neurons.
The findings also suggest abnormal neuron function in schizophrenia affects many brain areas, which could explain its diverse symptoms.
The team co-ordinated 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 is also published in Nature.
This study examined very rare mutations that have large effects on the small proportion of people that carry them, and researchers found overlapping genes and overlapping aspects of biology.
Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature 6 April 2022
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