Published Dec. 10 in Nature, a genomic analysis of more than 1 million people shows that most psychiatric risk variants overlap across disorders. The study groups 14 conditions into five genomic factors—Compulsive, Neurodevelopmental, Internalizing, Substance Use, and Schizophrenia–Bipolar—each with distinct biological signatures in the brain. Experts say these shared genetics point to common pathways that might guide cross-disorder treatments, but caution that genetic association is not proof of causation and that environmental factors shape outcomes.
Major Genomic Study Identifies Five Shared Genetic Signatures Across 14 Psychiatric Disorders
A new study groups 14 psychiatric disorders into five distinct genetic "factors.". | Credit: TEK IMAGE/SCIENCE PHOTO LIBRARY via Getty Images
A large new genomic analysis finds that most genetic variants linked to psychiatric conditions are shared across multiple diagnoses rather than confined to one. Published Dec. 10 in Nature, the study analyzed genetic data from more than 1 million people (predominantly of European ancestry) and grouped 14 psychiatric disorders into five distinct genomic factors, offering evidence of overlapping biological pathways that may underlie multiple mental health conditions.
Five Genomic Groups
The researchers measured genetic correlations between disorders and identified five clusters of shared genetic variation:
- Compulsive: Anorexia nervosa, obsessive-compulsive disorder (OCD), Tourette's syndrome.
- Neurodevelopmental: Autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD).
- Internalizing: Major depression, post-traumatic stress disorder (PTSD), anxiety disorders.
- Substance Use: Alcohol use disorder, cannabis use disorder, nicotine dependence, opioid dependence.
- Schizophrenia–Bipolar: Schizophrenia and bipolar disorder show strong genetic overlap.
Biological Signatures And Brain Cells
Each genomic factor exhibited distinct biological patterns when mapped to brain tissue. For example, genes associated with the schizophrenia–bipolar factor were especially active in excitatory neurons and brain regions involved in perception and interpretation of reality. By contrast, genes linked to the internalizing factor were enriched in glial cells—non-neuronal support cells involved in immune functions and maintaining neural connections—suggesting different cellular pathways may contribute to different clusters of disorders.
Broader Trait Associations And Ethical Considerations
The study also found that many psychiatric risk variants associate with other traits, including cognitive measures, sleep problems (such as insomnia), personality and social behaviors (for example, aggression), and socioeconomic outcomes. As geneticist Abdel Abdellaoui notes, some overlapping variants are connected to positive attributes—creativity or persistence—highlighting that genetic effects can be pleiotropic (influencing multiple traits).
"Psychiatric disorders often reflect extremes along natural genetic continua and may emerge when genetic predispositions interact with life experiences or environmental stressors," Abdellaoui wrote in a Nature commentary.
Those complexities matter for applications such as embryo selection in IVF, where parents may use polygenic risk scores to choose embryos with lower estimated risk for psychiatric conditions. Experts caution that polygenic scores are probabilistic, not deterministic, and that reducing risk for one outcome could affect other traits.
Expert Cautions
Chunyu Liu, a professor of psychiatry and behavioral sciences who was not involved in the work, said the results fit prior expectations—particularly the overlap between schizophrenia and bipolar disorder—but emphasized limits. "Genetic associations point to shared biology but do not by themselves explain why clinical symptoms differ across disorders," Liu said. He reminded readers that association does not equal causation and that additional mechanistic studies are required to demonstrate direct causal roles for specific genes or pathways.
The study advances understanding of the shared genetics of psychiatric disorders and highlights potential targets for treatments that could address biological mechanisms common to multiple conditions. The authors and commentators stress the need for further research, especially in more diverse populations, and for careful interpretation of genetic findings in clinical or reproductive settings.
Note: This article is informational and is not medical advice.
