A global genetics analysis has found extensive shared DNA risk across 14 psychiatric disorders, offering a clearer explanation for why many people receive multiple diagnoses over their lifetime. Using genomic data from more than six million individuals, researchers reported that the disorders cluster into five partially overlapping genetic groupings. The study was published Dec. 10, 2025, in Nature.
A large international genetics study has reported that many psychiatric disorders share substantial genetic risk, helping explain why comorbidity—having more than one diagnosis—is common.
The research was led by the Psychiatric Genomics Consortium’s Cross-Disorder Working Group and was supervised by Kenneth S. Kendler of Virginia Commonwealth University and Jordan W. Smoller of Harvard Medical School, according to a summary released by Virginia Commonwealth University.
Data and main findings
Researchers analyzed genetic association data drawn from more than six million people, including about 1.06 million cases across the disorders studied and roughly five million controls without diagnosed conditions in the datasets described in the reports.
Across the 14 disorders, the team reported widespread genetic overlap and identified five underlying genomic factors that captured much of the shared genetic structure across conditions. In the Nature paper, the authors report 238 “pleiotropic” loci associated with these genomic factors and describe 101 genomic regions showing correlated effects across disorders.
A Virginia Commonwealth University summary of the work separately describes 428 shared genetic variants and the same 101 chromosomal “hot spots,” reflecting results highlighted in the institution’s release.
Five genetic groupings
Based on genetic similarity, the disorders were organized into five broad groups:
- Compulsive factor: obsessive–compulsive disorder and anorexia nervosa, with Tourette’s syndrome and anxiety disorders showing weaker loading.
- Internalizing factor: major depression, post-traumatic stress disorder (PTSD), and anxiety disorders.
- Neurodevelopmental factor: autism spectrum disorder and attention-deficit/hyperactivity disorder (ADHD), with Tourette’s syndrome showing weaker loading.
- Schizophrenia–bipolar (SB) factor: schizophrenia and bipolar disorder.
- Substance use (SUD) factor: alcohol-use disorder, cannabis-use disorder, opioid-use disorder, and nicotine dependence.
Degree of overlap and cell-type links
In the Virginia Commonwealth University release, major depression, anxiety disorders and PTSD are described as sharing about 90% of their genetic risk, while schizophrenia and bipolar disorder are described as sharing roughly 66%.
The Nature paper also reports that shared genetic signals map to different brain cell types across groupings, including enrichment in genes expressed in excitatory neurons for the schizophrenia–bipolar factor and links to oligodendrocyte biology for the internalizing factor.
Implications
Kendler said the lack of definitive laboratory tests in psychiatry makes genetic approaches useful for clarifying how disorders relate to one another. “Psychiatry is the only medical specialty with no definitive laboratory tests,” he said in the Virginia Commonwealth University release, adding that clinicians largely rely on symptoms and signs rather than blood tests.
Kendler also described the project as a highly collaborative effort and said the findings could help inform how psychiatric disorders are defined and, eventually, how treatments are developed or adapted for conditions that commonly co-occur.
The study was published in Nature as “Mapping the genetic landscape across 14 psychiatric disorders” (DOI: 10.1038/s41586-025-09820-3).
