A large-scale genetic analysis suggests that many psychiatric diagnoses rest on a smaller set of shared biological factors than clinical categories imply. Drawing on DNA data from more than six million people worldwide, researchers report that common genetic signals cut across conditions long treated as distinct.
The study, published in Nature, was led by investigators at the University of Colorado Boulder and Mass General Brigham, working with the Psychiatric Genomics Consortium Cross-Disorder Working Group. The team analyzed genomes from over one million individuals diagnosed with at least one of 14 psychiatric disorders, alongside data from five million people without diagnoses.
“Right now, we diagnose psychiatric disorders based on what we see in the room, and many people will be diagnosed with multiple disorders. That can be hard to treat and disheartening for patients,” said Andrew Grotzinger, an assistant professor of psychology and neuroscience at CU Boulder and a corresponding author. “This work provides the best evidence yet that there may be things that we are currently giving different names to that are actually driven by the same biological processes.”
Using cross-disorder genomic modeling, the researchers identified five underlying genomic factors involving 238 variants. These factors grouped disorders into categories marked by shared genetic architecture, including compulsive conditions such as anorexia nervosa and obsessive-compulsive disorder, internalizing conditions like depression and anxiety, substance use disorders, neurodevelopmental conditions including autism and attention-deficit hyperactivity disorder, and a category linking bipolar disorder with schizophrenia.
“Genetically, we saw that they are more similar than they are unique,” Grotzinger said of the latter pairing. About 70 percent of the schizophrenia-associated genetic signal overlapped with bipolar disorder.
The analysis also connected disorder groupings to specific cell types and pathways. Variants affecting excitatory neurons were enriched in bipolar disorder and schizophrenia, while internalizing conditions showed associations with genes active in oligodendrocytes. Jordan Smoller of Mass General Brigham noted that “these findings provide valuable clues for advancing our understanding and treatment of mental illness with greater precision.”
Publication Details
Grotzinger, A.D., Werme, J., Peyrot, W.J. et al. Mapping the genetic landscape across 14 psychiatric disorders. Nature (2025). https://doi.org/10.1038/s41586-025-09820-3
The study, published in Nature, was led by investigators at the University of Colorado Boulder and Mass General Brigham, working with the Psychiatric Genomics Consortium Cross-Disorder Working Group. The team analyzed genomes from over one million individuals diagnosed with at least one of 14 psychiatric disorders, alongside data from five million people without diagnoses.
“Right now, we diagnose psychiatric disorders based on what we see in the room, and many people will be diagnosed with multiple disorders. That can be hard to treat and disheartening for patients,” said Andrew Grotzinger, an assistant professor of psychology and neuroscience at CU Boulder and a corresponding author. “This work provides the best evidence yet that there may be things that we are currently giving different names to that are actually driven by the same biological processes.”
Using cross-disorder genomic modeling, the researchers identified five underlying genomic factors involving 238 variants. These factors grouped disorders into categories marked by shared genetic architecture, including compulsive conditions such as anorexia nervosa and obsessive-compulsive disorder, internalizing conditions like depression and anxiety, substance use disorders, neurodevelopmental conditions including autism and attention-deficit hyperactivity disorder, and a category linking bipolar disorder with schizophrenia.
“Genetically, we saw that they are more similar than they are unique,” Grotzinger said of the latter pairing. About 70 percent of the schizophrenia-associated genetic signal overlapped with bipolar disorder.
The analysis also connected disorder groupings to specific cell types and pathways. Variants affecting excitatory neurons were enriched in bipolar disorder and schizophrenia, while internalizing conditions showed associations with genes active in oligodendrocytes. Jordan Smoller of Mass General Brigham noted that “these findings provide valuable clues for advancing our understanding and treatment of mental illness with greater precision.”
Publication Details
Grotzinger, A.D., Werme, J., Peyrot, W.J. et al. Mapping the genetic landscape across 14 psychiatric disorders. Nature (2025). https://doi.org/10.1038/s41586-025-09820-3