Large study identifies more than 100 genetic regions linked to schizophrenia

A team of researchers led by scientists from the Icahn School of Medicine at Mount Sinai, SUNY Downstate Health Sciences University, and the Department of Veterans Affairs has conducted the largest and most comprehensive genome-wide association study (GWAS) to date of schizophrenia in individuals of African ancestry. The study, published January 21 in Nature, identified more than 100 genetic regions associated with schizophrenia that had not been clearly identified in prior research. Importantly, the findings demonstrate that while specific genetic variants may differ across populations, the core biological mechanisms underlying schizophrenia are shared worldwide.

Schizophrenia affects people across all regions and backgrounds, yet most genetic studies to date have focused on individuals of European ancestry. This imbalance has limited scientific understanding of the disorder and reduced the accuracy of genetic tools for millions of people, particularly those of African ancestry.

“Our goal was to address a major gap in psychiatric genetics,” said Panos Roussos, MD, PhD, Professor of Psychiatry, and Genetic and Genomic Sciences, and Director of the Center for Disease Neurogenomics at the Icahn School of Medicine at Mount Sinai; Director of the Center for Precision Medicine and Translational Therapeutics at the James J. Peters VA Medical Center; and senior author of the study. “By expanding representation in genetic research, we not only discovered new schizophrenia-associated regions, but also gained a clearer picture of the shared biological pathways that drive the illness across populations.”

Key findings

Researchers found more than 100 new regions in the human genome linked to schizophrenia that had not been clearly identified before. Many of these genetic differences are more common in people of African ancestry, which explains why they were missed in earlier studies that mostly included people of European ancestry.

Even though some genetic differences vary by ancestry, the study found that schizophrenia affects the same underlying brain systems across populations. In other words, people around the world may carry different genetic “spelling changes,” but those changes tend to disrupt the same genes and the same brain cells. These cells work together to keep brain signals balanced, and disruptions in this balance appear to be central to schizophrenia.

These results give us confidence that schizophrenia is biologically similar across populations. At the same time, they also show how much we gain when genetic research includes people from diverse backgrounds.”

Dr. Panos Roussos, MD, PhD, Professor of Psychiatry, and Genetic and Genomic Sciences, Mount Sinai

Why this matters

The study underscores the scientific and ethical necessity of including diverse populations in genetic research. Broader representation not only uncovers ancestry-specific risk regions, but also strengthens confidence in universal biological mechanisms.

By identifying convergent genes, pathways, and brain cell types, the findings provide a stronger foundation for developing biology-informed therapies and genetic tools that are more equitable and applicable across populations.

The researchers emphasized that these genetic discoveries do not diagnose schizophrenia and do not determine who will or will not develop the disorder. “Genetic findings inform biology and research, but do not predict who will or will not develop the illness,” the authors stressed. “Environmental, social, and cultural factors also play critical roles in mental health and are not captured by genetic studies alone.”

While this study represents a major advance, the authors stress that larger and more diverse datasets, particularly from populations of African ancestry, are still urgently needed. Future work will focus on expanding global representation, refining the causal genes and cell types identified, and integrating genetic discoveries with functional studies in human brain tissue. A long-term goal of this research is translating shared biological insights into novel, mechanism-based treatments that can benefit individuals with schizophrenia worldwide.