Schizophrenia is a severe psychiatric disorder, and while it is characterized by certain behavioral and cognitive symptoms, there can be considerable differences in the presentation from one patient to another. Thousands of small changes in genes have been associated with the disease, so the biological causes may also vary considerably from one person to another. Researchers have now identified eight novel schizophrenia-linked genes, which may provide new insights into this complex and difficult-to-treat disease. The findings have been reported in Nature Communications.
In this work, the investigators used genetic data from almost 30,000 schizophrenia patients; over 100,000 people without the disorder, and 3,444 families with members with schizophrenia. The researchers were focused on finding rare, schizophrenia-associated mutations that had a large effect, and which arose in genes that code for protein.
This effort identified STAG1 and ZNF136 as genes that are strongly linked to schizophrenia risk when they carry mutations. Another six genes: BSCL2, CGREF, SLC6A1, KLC1, PCLO, and ZMYND11 were also discovered, but with a moderate link to schizophrenia risk.
"These findings are informative because they suggest that schizophrenia might be linked to changes in how DNA is organized within cells, and also disruptions in how brain cells communicate using a chemical called GABA,” said first study author Sophie Chick, a Cardiff University graduate student. "These results further our understanding of the complex neurobiology of schizophrenia and put us closer to the goal of advancing drug discovery and improving treatment."
The study also confirmed a hypothesis that neurodevelopment disorders and schizophrenia have some shared genetic architecture. For example, STAG1, SLC6A1, ZMYND11, and CGREF1 have been linked to autism spectrum disorder, epilepsy, and developmental delay in previous research.
"Rare genetic variants have long been known to have a role in schizophrenia, but identifying specific genes linked to these mutations has been a major challenge,” said corresponding study author Dr. Elliott Rees of Cardiff University School of Medicine. "Our findings represent an important step forward by expanding the number of genes now confidently associated with rare variants in the disorder. These genes and mutations provide a blueprint for future research aimed at uncovering the specific disease mechanisms that underlie schizophrenia disorder."
Sources: Cardiff University, Nature Communications