Shared Genetic Roots Uncover Interconnectedness of Psychiatric Disorders
A groundbreaking study by the Psychiatric Genomics Consortium (PGC) has revealed a surprising connection among 14 psychiatric disorders, suggesting that they share a common genetic basis. This finding challenges the traditional view of these disorders as distinct and separate conditions, instead pointing to a unified biological landscape.
The research, published in Nature, analyzed genome-wide data from a diverse range of childhood- and adult-onset psychiatric disorders, including depression, anxiety, schizophrenia, bipolar disorder, PTSD, OCD, eating disorders, substance use disorders, ADHD, autism, and Tourette syndrome. By employing advanced genomic techniques, the scientists explored how genetic variations are distributed across these disorders, cell types, and biological pathways.
Five Core Genetic Dimensions
The study's central discovery is the identification of five underlying "genomic factors" that account for a significant portion of the inherited risk across the 14 disorders. These factors represent broad dimensions of shared genetic vulnerability:
- Compulsive Disorders (OCD, anorexia nervosa, Tourette syndrome)
- Schizophrenia-Bipolar Disorders
- Neurodevelopmental Disorders (ADHD, autism)
- Internalizing Disorders (depression, anxiety, PTSD)
- Substance Use Disorders (alcohol, opioid, nicotine, cannabis)
These five factors collectively explained two-thirds of the genetic risk for the individual disorders, indicating that different psychiatric diagnoses often reflect variations on shared inherited pathways rather than entirely separate conditions.
Identifying "Hotspots" of Shared Genetic Risk
On a genomic level, the researchers identified over 100 regions of the genome where genetic variants influence multiple disorders simultaneously. One region on chromosome 11 emerged as a "hotspot," associated with eight of the 14 disorders and containing genes previously linked to addiction and other psychiatric traits.
In total, the study uncovered 428 genetic loci contributing to cross-disorder risk, with 268 loci directly tied to the five genomic factors.
Insights into Brain Biology
By integrating genetic findings with data from developing and adult human brain tissue, the study revealed specific biological processes and cell types implicated across disorders. These insights include:
- Shared genetic risk across all disorders was linked to fundamental biological processes involved in regulating gene expression, particularly active during early brain development.
- The schizophrenia and bipolar disorder factor was associated with genes active in excitatory neurons, including certain types of hippocampal neurons.
- The internalizing factor (depression, anxiety, PTSD) showed enrichment in genes active in oligodendrocytes, cells involved in brain connectivity.
Toward a More Biology-Based Understanding of Mental Health
The findings provide compelling evidence that psychiatric disorders share substantial genetic foundations that transcend current diagnostic boundaries. They also offer new avenues for developing treatments that target risk pathways common to frequently co-occurring conditions.
Statements from the Research Team
"Our study, the largest and most comprehensive cross-disorder analysis in psychiatric genetics to date, demonstrates that many psychiatric disorders share a broad genetic foundation, captured by five core genomic factors," said Oleksandr Frei, a shared first author of the study and researcher at the Centre for Precision Psychiatry, University of Oslo.
"By integrating multiple analytic approaches, we obtained a clearer understanding of the common and divergent effects of genetic variants across these disorders, refining diagnostic boundaries and providing new insights into the biological processes underlying psychiatric conditions," Frei added.
"This study brings us closer to a biologically informed map of mental illness, and highlights pathways that could guide future research, prevention, and therapeutics," the authors noted.
Source:
Journal reference: Grotzinger, A. D., et al. (2025). Mapping the genetic landscape across 14 psychiatric disorders. Nature. doi: 10.1038/s41586-025-09820-3. https://www.nature.com/articles/s41586-025-09820-3
