Psychiatric Disorders Share Far More DNA Than Scientists Realized

A global research team co-led by VCU expert Kenneth Kendler has produced the most comprehensive genetic map so far, identifying five families of disorders that show a high degree of overlap.

An international team of scientists is offering new insight into why people are so often affected by more than one psychiatric condition. In a study published on December 10 in the journal Nature, the researchers present the most extensive analysis so far of shared genetic influences across 14 mental health disorders.

The work comes from the Psychiatric Genomics Consortium’s Cross-Disorder Working Group and is co-chaired by Kenneth Kendler, M.D., a professor of psychiatry at Virginia Commonwealth University’s School of Medicine, and Jordan Smoller, M.D., a professor of psychiatry at Harvard Medical School.

Why psychiatric disorders rarely occur alone

Most individuals diagnosed with a psychiatric disorder will later receive at least one additional diagnosis during their lifetime, complicating both diagnosis and treatment. Although life experiences and environmental factors shape this risk, inherited genetic factors also contribute substantially.

Using genetic data from more than 6 million people, the research team charted the shared genetic structure of 14 psychiatric conditions. Their analysis identified five major groups of disorders that share large portions of genetic risk. These findings represent a key advance in understanding how different psychiatric conditions are biologically connected and may help guide more effective clinical care.

“Psychiatry is the only medical specialty with no definitive laboratory tests. We can’t give a blood test to tell whether someone has depression – we have to rely on symptoms and signs. And that’s true for almost every psychiatric disorder,” said Kendler, a world-renowned researcher for his pioneering studies in psychiatric genetics. “Genetics is a developing tool that allows us to understand the relationships between disorders. The findings from this study reflect the most comprehensive analysis of psychiatric genomic data to date and shed new light on why individuals with one psychiatric disorder often have a second or third.”

Mining millions of genomes for shared risk

To conduct the study, researchers examined genetic information from more than 1 million people diagnosed with a psychiatric disorder during childhood or adulthood, along with data from 5 million individuals without such diagnoses. By identifying genetic variants that appear more frequently in people with specific conditions, the team was able to pinpoint genetic factors that contribute to psychiatric disease and reveal patterns of shared risk across disorders.

The working group then used multiple complementary analytic approaches to dissect the genetic architecture of 14 psychiatric disorders and identify conditions with high genetic overlap. Their analysis identified 428 genetic variants associated with more than one disorder, as well as 101 regions on chromosomes that were “hot spots” for these shared genetic variants.

Five genetic families of psychiatric disorders

Through statistical modeling, the researchers found that the 14 disorders could be divided into these five groups based on genetic similarities:

• Compulsive disorders include obsessive compulsive disorder and anorexia nervosa, with Tourette disorder and anxiety disorders also showing genetic links, though to a lesser degree.
• Internalizing disorders consist primarily of major depression, anxiety disorders, and post-traumatic stress disorder.
• Neurodevelopmental disorders include autism spectrum disorder and attention deficit hyperactivity disorder, with Tourette disorder again showing weaker genetic overlap.
• Schizophrenia and bipolar disorder formed their own closely related group.
• Substance use disorders include opioid use disorder, cannabis use disorder, alcohol use disorder, and nicotine dependence.

Major depression, anxiety, and post-traumatic stress disorder showed especially high levels of genetic overlap, with about 90% of genetic risk estimated to be shared across these three conditions. Schizophrenia and bipolar disorder share about 66% of their genetic markers.

Shared genes, shared brain biology

Through this study, the researchers also discovered that disorders with high genetic overlap also showed similarities related to when shared genes were expressed during human development and which brain cell types were impacted. For example, genes expressed in oligodendrocytes, a key part of the central nervous system, were more prominent in internalizing disorders, while genes expressed in excitatory neurons, which activate other neurons, were more prominent in schizophrenia and bipolar disorder.

The researchers say these findings provide a solid scientific basis for how the psychiatric field defines disorders, and the study could inform future efforts to create or repurpose therapeutics to treat conditions that commonly occur together.

“I feel very proud to be a part of this effort,” Kendler said. “This work really shows that we gain more for our field and for those suffering from mental illness when we come together to tackle these scientific challenges.”

Reference: “Mapping the genetic landscape across 14 psychiatric disorders” by Andrew D. Grotzinger, Josefin Werme, Wouter J. Peyrot, Oleksandr Frei, Christiaan de Leeuw, Lucy K. Bicks, Qiuyu Guo, Michael P. Margolis, Brandon J. Coombes, Anthony Batzler, Vanessa Pazdernik, Joanna M. Biernacka, Ole A. Andreassen, Verneri Anttila, Anders D. Børglum, Gerome Breen, Na Cai, Ditte Demontis, Howard J. Edenberg, Stephen V. Faraone, Barbara Franke, Michael J. Gandal, Joel Gelernter, Alexander S. Hatoum, John M. Hettema, Emma C. Johnson, Katherine G. Jonas, James A. Knowles, Karestan C. Koenen, Adam X. Maihofer, Travis T. Mallard, Manuel Mattheisen, Karen S. Mitchell, Benjamin M. Neale, Caroline M. Nievergelt, John I. Nurnberger, Kevin S. O’Connell, Roseann E. Peterson, Elise B. Robinson, Sandra S. Sanchez-Roige, Susan L. Santangelo, Jeremiah M. Scharf, Hreinn Stefansson, Kari Stefansson, Murray B. Stein, Nora I. Strom, Laura M. Thornton, Elliot M. Tucker-Drob, Brad Verhulst, Irwin D. Waldman, G. Bragi Walters, Naomi R. Wray, Dongmei Yu, Anxiety Disorders Working Group of the Psychiatric Genomics Consortium, Attention-Deficit/Hyperactivity Disorder (ADHD) Working Group of the Psychiatric Genomics Consortium, Autism Spectrum Disorders Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Eating Disorders Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Nicotine Dependence GenOmics (iNDiGO) Consortium, Obsessive-Compulsive Disorder and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium, Post-Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, Phil H. Lee, Kenneth S. Kendler and Jordan W. Smoller, 10 December 2025, Nature.
DOI: 10.1038/s41586-025-09820-3

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