What is the role of genetics in schizophrenia? To address this question, an international group of researchers developed and conducted the largest-ever genetic study on schizophrenia. As part of their work, the researchers identified a large number of specific genes which play a key role in the onset and development of this mental disorder. Their findings have now been published in Nature.
Schizophrenia is a serious mental disorder which usually develops during late adolescence or early adulthood. According to the World Health Organization, the disorder affects approximately one in 300 people. Symptoms of schizophrenia include altered perceptions and abnormal thinking, difficulty concentrating, hallucinations, delusions, and lack of motivation. Even today, our understanding of this complex condition remains inadequate. Current hypotheses suggest the interplay of multiple factors; in addition to genetic predisposition (which plays a key role in pathogenesis), the disorder is also thought to have neurobiological and psychosocial components.
“That genetic causes play a major role has been known for decades. However, many mechanisms remain to be fully elucidated. Our investigation looked for specific genes and gene sections which are implicated in heritability. This enabled us to draw conclusions about biological processes and potential new treatments for this disorder,” explains one of the study’s co-last authors. The current study, which involved hundreds of researchers from 45 countries analyzing the DNA of 76,755 people with schizophrenia and 243,649 without schizophrenia, enabled the consortium to shed more light on the genetic basis of schizophrenia.
This large-scale, genome-wide association study compared the genomes (i.e., the DNA blueprint for the human body) of thousands of individuals in order to detect associations with a specific trait or disease. The researchers’ aim was to identify sections of DNA which are linked with schizophrenia, i.e., sections which are ‘associated’ with a predisposition for the disorder.
Overall, a total of 287 genomic regions were found to be associated with schizophrenia. Previous studies had identified just 100 such DNA regions. Using state-of-the-art analytical techniques to explore these regions in greater detail, the researchers discovered 120 specific genes likely to be implicated in the development of this mental disorder.
“We had already identified associations between specific genetic regions and the risk of developing schizophrenia during earlier studies, but were unable to interpret their biological functions,” explains one the study’s co-first authors, and continues: “That is what we were able to do in this study. Not only did we succeed in finding a larger number of these associations, but we were also able to link many of them to specific genes and biological signaling pathways, identifying them as schizophrenia-relevant.”
The researchers were also able to identify neurons – a special type of nerve cell in the brain – as the source of a person’s genetic risk of schizophrenia. The researchers’ findings suggest that unusual neuronal function affects many different areas of the brain, and that this might explain the different symptoms of schizophrenia.
https://www.nature.com/articles/s41586-022-04434-5
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fmapping-genomic-loci&filter=22
More genes implicated in schizophrenia synaptic biology identified
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