An article published in Nature by a consortium of researchers from 45 countries, including Brazil, reports on a study that analyzed data for 300,000 people and could pave the way for the development of novel therapies (image: Pixabay)

Published on 04/25/2022

By André Julião  |  Agência FAPESP – A study published on April 8 in the journal Nature by an international consortium of scientists found at least 120 genes associated with schizophrenia. FAPESP supported the research in Brazil.

The group, which includes researchers at the Federal University of São Paulo (UNIFESP) in Brazil, demonstrated a causal relationship between these genes and the development of this mental disorder by analyzing the DNA of some 300,000 people.

It was the largest-ever genetic study of schizophrenia, which affects some 24 million people worldwide and more than 2 million in Brazil. 

“Schizophrenia has a larger polygenic contribution [influenced by more than one gene] than was thought. The study identified 120 genes associated with the disease, all of them acting on neurons. This shows the key role played by neurons in schizophrenia and paves the way for the development of novel therapies,” Sintia Belangero, a co-author of the article, told Agência FAPESP. 

Belangero is a professor at UNIFESP’s Medical School (EPM). She and the other co-authors are members of the Schizophrenia Working Group (SWG) of the Psychiatric Genomics Consortium (PGC), set up in 2007 to conduct mega-analyses of genome-wide genetic data for psychiatric disorders. SWG-PGC is led by scientists affiliated with Cardiff University in Wales.

The Brazilian team also includes Ary Gadelha, Rodrigo Bressan, Quirino Cordeiro and Cristiano Noto, all of whom are professors at EPM-UNIFESP; Marcos Santoro, a professor in UNIFESP’s Biochemistry Department; Vanessa Ota, a biomedical researcher at UNIFESP; and Paulo Menezes and Cristina Del-Ben, affiliated with the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP).

The 120 genes identified in the study are located in 287 regions of the human genome that have only now been associated with schizophrenia. Previous research by the group had pointed to only 108 regions linked to the disease. More advanced methods were used in this latest study, and the number of samples analyzed was larger than in any previous study.

The group analyzed DNA data for 76,755 people with schizophrenia and 243,649 without the disease. The aim was to achieve a better understanding of the genes and biological processes associated with schizophrenia. The Brazilian cohort comprised more than 600 volunteers, contributing to the diversity of samples in the study.

Global surveys of the kind rarely include people with non-European ancestry, making the results obtained now more likely to benefit Latinos and people of African descent. In the next five years, under Gadelha’s leadership, UNIFESP plans to collect more than 20,000 samples for inclusion in future studies in the next five years.

Causal link

Genetic factors appear to be linked to between 60% and 80% of the origin of schizophrenia. The recently published study shows, however, that up to 24% can be attributed to single nucleotide variants (SNVs), DNA sequence variations that occur whenever a single nucleotide (adenine, thymine, cytosine, or guanine) in the genome sequence is altered.

Other genetic and environmental factors may contribute to development of the disease. Patients do not always respond well to the existing treatments.

Previous research had shown links between schizophrenia and DNA sequences, but specific genes had been identified in only a few studies. Now researchers all over the world have a list of genes to analyze in depth so that knowledge of the disease can be advanced.

“Schizophrenia continues to be a complex and heterogeneous disease, but this study has opened up the possibility of new approaches to treatment,” Belangero said. “For example, we can now study these 120 genes at length and explore the functional involvement of each one in the disease. It’s only a start, but a very promising one.”

The study received funding from FAPESP via seven projects (10/08968-6, 14/07280-1, 07/58736-1, 16/04983-7, 10/19176-3, 12/05178-0 and 12/12686-1).

The article “Mapping genomic loci implicates genes and synaptic biology in schizophrenia” is at: www.nature.com/articles/s41586-022-04434-5.

 

Source: https://agencia.fapesp.br/38467