Researchers from the Psychiatric Genomics Consortium (PGC) report that most genetic influences on mental illness are shared across diagnostic categories, revealing a more interconnected biological landscape than traditional classifications suggest.

The study analyzed genome-wide data for 14 childhood- and adult-onset psychiatric disorders, including depression, anxiety, schizophrenia, bipolar disorder, PTSD, OCD, eating disorders, substance use disorders, ADHD, autism, and Tourette syndrome. Using multiple cutting-edge genomic methods, the researchers examined how genetic variation is distributed across disorders, cell types, and biological pathways.

Five Core Genetic Dimensions of Mental Illness
A central finding is that the majority of inherited risk across the 14 disorders can be attributed to five underlying “genomic factors.” These represent broad dimensions of shared genetic vulnerability:

1. Compulsive Disorders (OCD, anorexia nervosa, Tourette syndrome)
2. Schizophrenia–Bipolar Disorders
3. Neurodevelopmental Disorders (ADHD, autism)
4. Internalizing Disorders (depression, anxiety, PTSD)
5. Substance Use Disorders (alcohol, opioid, nicotine, cannabis)

These five factors together accounted for two-thirds of the genetic risk for the individual disorders - evidence that different psychiatric diagnoses often reflect variations on shared inherited pathways rather than completely distinct conditions.

“Hotspots” of Shared Genetic Risk Identified
At the genomic level, the researchers identified over 100 regions of the genome where genetic variants influence multiple disorders simultaneously. One region on chromosome 11 stood out as a “hotspot,” showing associations 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 that contribute to cross-disorder risk, including 268 loci tied directly to the five genomic factors.

Insights Into Brain Biology
By integrating the genetic findings with data from developing and adult human brain tissue, the study points to specific biological processes and cell types implicated across disorders:

• Shared, broad 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 one of the clearest indications yet that psychiatric disorders share substantial genetic foundations that cut across current diagnostic boundaries. They also offer new entry points 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 - shows that many psychiatric disorders share a broad genetic foundation, captured by five core genomic factors,” says 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 adds.

“This study brings us closer to a biologically informed map of mental illness,” the authors note, “and highlights pathways that could guide future research, prevention, and therapeutics.”