Summary: A large-scale genetic analysis reveals extensive overlap in genetic risk across several psychiatric disorders. Around 70% of the genetic signals linked to schizophrenia also associate with bipolar disorder, while anorexia nervosa and obsessive-compulsive disorder share a strong genetic foundation. These shared genetic patterns help explain why co-occurring psychiatric diagnoses are common.
Source: University of Colorado
More than half of people diagnosed with one psychiatric disorder will go on to receive a second or third diagnosis in their lifetime; roughly one in three will receive four or more.
This high rate of comorbidity complicates treatment and can leave people feeling frustrated and overwhelmed. A comprehensive new genetic study, however, sheds light on why multiple diagnoses frequently occur together and suggests paths toward more integrated clinical approaches.
Published in Nature Genetics, the analysis examined common genetic variation across 11 major psychiatric disorders. The researchers found that, while there is no single gene or single set of genes responsible for risk across all conditions, distinct subsets of disorders share substantial portions of their genetic architecture. Notable clusters include bipolar disorder with schizophrenia; anorexia nervosa with obsessive-compulsive disorder (OCD); and major depressive disorder with anxiety disorders.
“Our findings confirm that high comorbidity across some disorders in part reflects overlapping pathways of genetic risk,” said lead author Andrew Grotzinger, an assistant professor in the Department of Psychology and Neuroscience. These results offer a biological explanation for frequent co-occurrence and may help guide future diagnostic frameworks and treatment strategies.
Grotzinger added that better mapping of biological risk could reduce fragmented diagnoses. “If you had a cold, you wouldn’t want to be diagnosed with coughing disorder, sneezing disorder and aching joints disorder,” he said. The study is a step toward a diagnostic manual that more closely reflects underlying biology rather than separate symptom-based labels.
Study design and methods
The team combined publicly available genome-wide association study (GWAS) data from hundreds of thousands of participants drawn from large datasets such as the UK Biobank and the Psychiatric Genomics Consortium. They analyzed genetic associations for 11 psychiatric conditions: schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, anorexia nervosa, obsessive-compulsive disorder, Tourette syndrome, post-traumatic stress disorder, problematic alcohol use, ADHD and autism.
Beyond GWAS data, the researchers incorporated wearable accelerometer measurements and survey-based biobehavioral traits to explore how shared genetic risk relates to real-world behavior and physiology. They applied novel statistical genetic methods, including stratified genomic structural equation modeling, to identify patterns of genetic overlap and the biological pathways that contribute to shared risk.
Key genetic overlaps and biobehavioral links
A striking result showed that about 70% of the genetic signal associated with schizophrenia also links to bipolar disorder. Although clinical practice often treats these as separate diagnoses, their genetic overlap suggests common underlying biology. The study also confirmed a strong genetic relationship between anorexia nervosa and OCD, and found that genetic predisposition to lower body mass index (BMI) correlates with genetic risk for these conditions.
Major depressive disorder and anxiety disorder demonstrated large genetic overlap, consistent with their frequent co-occurrence. When comparing genetic results with accelerometer data, the researchers observed that disorders that cluster genetically often share genes influencing daily movement patterns. Internalizing disorders such as anxiety and depression correlate genetically with lower daytime activity, compulsive conditions like OCD and anorexia associate with higher overall movement, and psychotic disorders (schizophrenia and bipolar disorder) show genetic links to increased early-morning activity.
The analysis identified 152 genetic variants shared across multiple disorders, including several variants already known to affect specific types of brain cells. Variants impacting excitatory and GABAergic neurons—cell types crucial to neural signaling—appear to underlie much of the shared genetic signal between schizophrenia and bipolar disorder.
Implications and next steps
While further research is required to determine exactly how the identified genes influence brain function and behavior, this work represents an important step toward therapies that could address multiple disorders through shared biological targets. Grotzinger noted that many patients are prescribed several medications to manage co-occurring diagnoses, which can increase side-effect burdens. Identifying common mechanisms may allow treatments that reduce the need for multiple drugs or separate interventions.
Beyond treatment, clearer genetic explanations can offer reassurance to individuals with complex diagnostic profiles. “It’s important for people to know they didn’t just get a terrible roll of the dice in life—that they are not facing multiple different issues but rather one set of risk factors bleeding into them all,” Grotzinger said.
About this genetics and mental health research news
Author: Press Office
Source: University of Colorado
Contact: Press Office – University of Colorado
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Original Research: Open access. “Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis” by Andrew D. Grotzinger et al., Nature Genetics
Abstract
Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis
The study interrogates the joint genetic architecture of 11 major psychiatric disorders across biobehavioral, functional genomic and molecular genetic levels. It identifies four broad genetic factors—neurodevelopmental, compulsive, psychotic and internalizing—that structure genetic correlations among these disorders and evaluates how these factors explain genetic links to biobehavioral traits.
Using stratified genomic structural equation modeling, the authors detect gene sets that disproportionately contribute to shared genetic risk, including protein-truncating variant-intolerant genes expressed in excitatory and GABAergic neurons enriched for overlap among psychotic-feature disorders. Multivariate analyses reveal 152 independent loci (20 novel) influencing the identified factors, and nine loci with heterogeneous effects across disorders within a factor. Despite moderate-to-high genetic correlations across the 11 disorders, the study finds limited utility for a single, overarching dimension of genetic risk across all psychiatric conditions at the levels of biobehavioral correlates or individual variants.