AI models map 766 schizophrenia-linked genes, most newly identified

Schizophrenia is one of the major puzzles of modern genetics. Unlike diseases caused by a single mutation, the disorder arises from a combination of hundreds of genetic variants, each exerting a modest effect on distinct brain processes. Some variants influence neuronal development, others alter inter-neuronal communication or the organization of synaptic connections. To decipher this architecture, scientists must determine not only the individual contributors but also how the genes interact and whether they form biological networks that amplify risk. Computational models based on artificial intelligence are required to reconstruct the coordinated activity of thousands of genes in the human brain.

A study published in Nature Genetics provides one of the most detailed pictures to date. The authors identified 766 genes associated with schizophrenia, of which 641 had not appeared in prior transcriptomic (RNA-activity) analyses. A large share of the genes were discovered through long-range regulatory signals, supporting the view that the disease-related genes operate as an interconnected network rather than isolated elements. The researchers likened the finding to lighting up an entire neighborhood: previously only a few houses were illuminated, now a much larger portion of the genetic risk map can be seen.

The investigation analysed genetic data from more than 102,000 individuals and brain-tissue samples from six regions obtained from hundreds of donors. Researchers from the Lieber Institute for Brain Development, the University of Bari, and dozens of psychiatric centers worldwide contributed to the project. The computational models were used to simulate the synchronized activity of thousands of genes, rather than merely pinpointing individual mutations. The variants act in concert and together contribute to risk; with part of this foundation exposed, scientists can probe disease behavior and potential treatments with greater precision.

The World Health Organization estimates that schizophrenia affects about 23 million people globally, roughly one in 345 individuals. Although experts have long recognised the importance of genetics, how the numerous biological factors interact remains unclear. A family history raises risk but does not determine it: some relatives of affected individuals never develop the disorder, while others are diagnosed without any known family history. The illness distorts perception, manifesting as hallucinations and delusional thoughts, and can also lead to social withdrawal, reduced motivation, attention problems, memory difficulties and thought disorders. This symptom diversity reflects the underlying complexity of biological mechanisms, indicating that no single gene is responsible but rather an extensive network of inter-dependent processes.