While mental disorders stem from a mix of biological and environmental factors, genetic influences explain part of their complexity. Yet genetics are still rarely used to inform diagnosis or treatment. An international team has now taken a major step toward charting these genetic connections. In the largest study of its kind, published in Nature, researchers compared common genetic variants across 14 psychiatric conditions, identifying five major clusters, or factors, that share overlapping genetic features.
“Psychiatric disorders have symptoms in common, which makes diagnosis difficult, as it’s still based solely on clinical evaluation,” says study participant Diego Luiz Rovaris of the University of São Paulo. He notes that the data support what clinicians have long observed: schizophrenia and bipolar disorder, for instance, share about 80% of their genetic variants, suggesting a continuum rather than fully distinct diseases.
Factor 1 includes compulsive and anxiety‑related conditions such as anorexia nervosa, obsessive‑compulsive disorder (OCD), Tourette syndrome, and anxiety disorders. Factor 2 comprises schizophrenia and bipolar disorder, which share gene expression patterns in excitatory neurons and brain regions that process reality. Factor 3 involves neurodevelopmental conditions—autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and to a lesser extent, Tourette syndrome—driven by genes active early in brain development.
Factor 4 includes internalizing conditions such as depression, generalized anxiety, and post‑traumatic stress disorder (PTSD). These are linked to genes expressed mainly in glial cells rather than neurons, pointing to the importance of brain support structures. Factor 5 concerns substance use, encompassing alcohol, nicotine, cannabis, and opioid dependence. Variants in genes that encode alcohol‑processing enzymes and nicotine receptors were prominent. This factor also showed the closest association with socioeconomic variables like cognitive ability and income, highlighting stronger environmental influences.
The analysis, covering over one million people, also revealed a “P factor” of genetic variants shared across all 14 disorders. Tourette syndrome stood out, as 87% of its genetic characteristics were unique.
According to co-author Sintia Belangero of the Federal University of São Paulo, the genetic association data from common variants robustly reinforced what other genetic evidence and clinical data had already suggested, allowing for further studies on psychiatric conditions and possibly guiding future therapies, including drug repurposing.
Publication details: Grotzinger, A.D., Werme, J., Peyrot, W.J. et al. Mapping the genetic landscape across 14 psychiatric disorders. Nature 649, 406–415 (2026). https://doi.org/10.1038/s41586-025-09820-3
“Psychiatric disorders have symptoms in common, which makes diagnosis difficult, as it’s still based solely on clinical evaluation,” says study participant Diego Luiz Rovaris of the University of São Paulo. He notes that the data support what clinicians have long observed: schizophrenia and bipolar disorder, for instance, share about 80% of their genetic variants, suggesting a continuum rather than fully distinct diseases.
Factor 1 includes compulsive and anxiety‑related conditions such as anorexia nervosa, obsessive‑compulsive disorder (OCD), Tourette syndrome, and anxiety disorders. Factor 2 comprises schizophrenia and bipolar disorder, which share gene expression patterns in excitatory neurons and brain regions that process reality. Factor 3 involves neurodevelopmental conditions—autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and to a lesser extent, Tourette syndrome—driven by genes active early in brain development.
Factor 4 includes internalizing conditions such as depression, generalized anxiety, and post‑traumatic stress disorder (PTSD). These are linked to genes expressed mainly in glial cells rather than neurons, pointing to the importance of brain support structures. Factor 5 concerns substance use, encompassing alcohol, nicotine, cannabis, and opioid dependence. Variants in genes that encode alcohol‑processing enzymes and nicotine receptors were prominent. This factor also showed the closest association with socioeconomic variables like cognitive ability and income, highlighting stronger environmental influences.
The analysis, covering over one million people, also revealed a “P factor” of genetic variants shared across all 14 disorders. Tourette syndrome stood out, as 87% of its genetic characteristics were unique.
According to co-author Sintia Belangero of the Federal University of São Paulo, the genetic association data from common variants robustly reinforced what other genetic evidence and clinical data had already suggested, allowing for further studies on psychiatric conditions and possibly guiding future therapies, including drug repurposing.
Publication details: Grotzinger, A.D., Werme, J., Peyrot, W.J. et al. Mapping the genetic landscape across 14 psychiatric disorders. Nature 649, 406–415 (2026). https://doi.org/10.1038/s41586-025-09820-3