A massive genetic analysis of more than 6 million people is revealing new clues about why mental health disorders frequently overlap.
An international group of scientists has uncovered new evidence explaining why many mental health disorders tend to occur together. By examining genetic data from more than 6 million people, the researchers explored how over a dozen psychiatric conditions may be connected, including depression, anxiety, schizophrenia, bipolar disorder, ADHD, PTSD, and substance use disorders.
The study, published in Nature, was co-authored by Drs. John Hettema and Brad Verhulst of the Texas A&M University Department of Psychiatry and Behavioral Sciences in the Naresh K. Vashisht College of Medicine.
Because of its massive scale, the research offers one of the clearest views so far of how genetic risk is shared across different psychiatric conditions. The team analyzed DNA data for 14 childhood and adult onset disorders. The dataset included more than 1 million people diagnosed with a psychiatric disorder and about 5 million people with none of the studied conditions.
Genetic links between mental health disorders
“Genetic risk” refers to the likelihood of developing a disease or health condition based on inherited variations in DNA.
The researchers found that the psychiatric disorders in the study share a substantial amount of genetic risk. These risks formed five broad categories:
- Compulsive disorders (like OCD and anorexia)
- Schizophrenia and bipolar disorder
- Neurodevelopmental disorders (such as autism and ADHD)
- Internalizing disorders (depression, anxiety, PTSD)
- Substance use disorders
These results suggest that the same genetic influences often affect multiple disorders. This overlap may help explain why people frequently experience more than one mental health condition.
The analysis showed that these five genetic groupings account for much of the shared risk among the disorders. Each group was associated with 238 genetic variants, small differences in DNA that can influence how the brain functions. These patterns may help researchers understand why certain conditions commonly appear together while others remain more distinct.
Several traits, including suicidality and loneliness, were also genetically connected to all five groups.
“These findings help explain why mental health conditions often overlap,” said Hettema, a professor and psychiatrist whose clinical and research expertise focuses on the epidemiology, genetics, and biology of anxiety and related disorders. “By uncovering shared genetic roots, we can start thinking about treatments that target multiple disorders instead of treating each one in isolation.”
Brain Cells Linked to Genetic Patterns
The study also identified specific brain cell types associated with the genetic patterns.
For the schizophrenia bipolar group, the strongest genetic signals appeared in genes active in excitatory neurons. These neurons transmit signals that activate other brain cells and help different parts of the brain communicate.
In contrast, genetic risk tied to internalizing disorders such as depression, anxiety, and PTSD showed stronger links to oligodendrocytes. These cells help nerve signals travel more efficiently through the brain.
“The findings suggest these ‘support cells’ might play an important role in those conditions,” said Verhulst, research assistant professor and an expert in quantitative and statistical genetics.
The big picture for mental health
Mental health conditions affect nearly half the population at some point in life. Yet most psychiatric diagnoses are still based on symptoms rather than underlying biology.
“This study moves us closer to a science-based classification system for mental illness that reflects underlying genetics,” Hettema said.
“It also opens the door to new treatments that target shared biological pathways, potentially helping people with several conditions at once.”
The researchers stress that genetics does not determine whether someone will develop a psychiatric disorder. As with common medical conditions such as hypertension and diabetes, genes influence risk but do not guarantee a specific outcome.
Instead, inherited genetic factors can raise or lower a person’s vulnerability, while environmental influences such as stress may trigger the development of illness.
The study highlights the importance of analyzing multiple disorders together rather than focusing on one condition at a time. By studying patterns across diagnoses, scientists can detect connections that might remain hidden in smaller, more narrowly focused research.
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
Funding: NIH/National Institute of Mental Health, NIH/National Institute on Drug Abuse, NIH/National Institute on Aging, Dutch Ministry of Education, Culture and Science, Autism Speaks, Tobacco-Related Disease Research Program, European Research Council, NIH/National Institute of Neurological Disorders and Stroke, Supernus Pharmaceuticals, Lundbeck Foundation, Research Council of Norway, NIH/National Institute of General Medical Sciences, NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development, Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, European Union Horizon 2020, Canadian Institutes of Health Research, NIHR Biomedical Research Centre, NIH/National Institute on Alcohol Abuse and Alcoholism, The Brain & Behavior Research Foundation
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