A groundbreaking study has mapped the genetic landscape of 14 psychiatric conditions.
Curator’s Note: A significant study published in Nature has explained the genetic landscape of 14 psychiatric conditions, utilizing data from over one million cases. It discovered five shared genetic factors accounting for two-thirds of the common genetic risk, leading to potential reevaluations of mental illness diagnoses and treatments. The study analyzed disorders including ADHD, schizophrenia, and major depression, revealing dynamic genetic correlations across conditions. It identified a general genetic risk factor influenced by internalizing issues as well as unique attributes linked to specific disorders. These insights could revolutionize mental health treatment and assessment by promoting a more integrated understanding of psychiatric conditions. This essay was written by Dr Khalid Rahman, a health scientist and clinical researcher.
An extensive study published in Nature may change how we understand mental health. The researchers mapped the genetic makeup of 14 primary psychiatric conditions using data from over 1 million cases.
The study found that five shared genetic factors explained about two-thirds of the common genetic risk for these conditions, with some effects unique to each disorder.
These results could challenge traditional ways of diagnosing mental illnesses and open the door to new treatments based on biology.
The 14 psychiatric disorders
The researchers used the most extensive available genome-wide association studies (GWAS) to look at these 14 psychiatric conditions in both children and adults.
- Attention-deficit/hyperactivity disorder (ADHD)
- Autism spectrum disorder
- Anorexia nervosa
- Obsessive-compulsive disorder (OCD)
- Tourette’s syndrome
- Schizophrenia
- Bipolar disorder
- Major depression
- Anxiety disorders
- Post-traumatic stress disorder (PTSD)
- Alcohol-use disorder
- Nicotine-dependence
- Opioid-use disorder
- Cannabis-use disorder
This study included about 2.6 times as many cases as earlier studies, an increase of almost 165%. This larger sample enabled the researchers to identify shared genetic patterns across different psychiatric conditions, rather than focusing on single genes for each disorder.
The 5 silent genomic attributes
The research team used structural equation modeling to identify five hidden genetic factors that explained how the 14 psychiatric disorders were connectedwith each other.
This research unboxed nearly 66% of the common variance observed across the genetic risk for these disorders, over and above the variance in the individual genes for each disease condition spanning the psychiatric disorders.
Here are the five genetic characteristics the study analyzed.
- Compulsive (related to OCD, Tourette syndrome, and the comparatively weaker anxiety) – The key features included control-oriented phenotypes and repetitive thoughts and behaviors.
- Schizophrenia-bipolar (covering schizophrenia and bipolar disorder) – The key attributes included shared genetic signals and very few unique loci.
- Neurodevelopmental (including Tourette’s syndrome, autism, and ADHD): This factor overlapped more with childhood aggression and body mass index (BMI).
- Internalizing (related to major depression, anxiety, and PTSD): This factor was mainly linked to stress sensitivity, neuroticism, self-harm, and suicide attempts.
- Substance-use disorders, including weaker connections to ADHD as well as to alcohol, nicotine, opioid, and cannabis use disorders.
The authors also identified a higher-level p-factor linked to general psychopathology. This factor was influenced by internalizing factors and reflected a broad vulnerability across diagnoses.
Let me simplify this further!
The researchers found one general genetic risk factor for mental illnesses that sits above the five more specific genetic factors.
This general factor is shaped mainly by genetic signals linked to internalizing problems like depression, anxiety, and PTSD. It also increases risk for several other psychiatric conditions.
Looking closer at brain cell types and genetic overlap
The authors of this landmark study conducted several complementary assessments that led them to the same conclusion:
A penetrating genome was observed across the analyzed psychiatric conditions.
The authors also estimated genetic correlations through linkage disequilibrium score regression (LDSC).
The results demonstrated dynamic positive associations between several pairs of psychiatric disorders, such as schizophrenia-bipolar, major depression-anxiety, and major depression-PTSD.
The MiXeR analysis found that most shared genetic variants raise the risk for several psychiatric conditions at once. So, having a genetic risk factor for one disorder often means a higher risk for others, too.
The researchers also examined specific genetic regions. They found 101 hotspots where the same genetic spot was linked to several psychiatric disorders.
They also noted an NCAM1-TTC12-ANKK1-DRD2 cluster (a prominent location on chromosome 11) that correlates with several behavioral and psychiatric traits.
The functional assessments revealed that many of the same genetic changes were seen across all of the analyzed mental disorders. And these changes appeared to influence the fundamental brain setup processes before birth and during the early years of life.
The authors observed dynamic genetic signals in excitatory neurons in deeper brain layers in relation to the schizophrenia-bipolar disorder factor.
They noted that the strongest signals across excitatory neurons, oligodendrocytes, and other glial cells were connected to the internalizing factor.
The researchers found that, although these psychiatric disorders affect different brain cell circuits, they have common genetic risk factors.
This is what makes the genetic insights from this study unique.
The researchers observed that several DNA spots were associated with broader patterns of psychiatric disease risk.
In fact, many of these DNA spots were overlooked or ignored when authors analyzed each psychiatric condition in isolation. This finding favors the strategy of analyzing several mental health conditions simultaneously to unbox their actual biology.
The authors then directly compared several combinations of psychiatric conditions. What they found was that the same DNA spots in the variants had similar trajectories and simultaneously impacted many mental disorders. This finding was more valid in the schizophrenia-bipolar pair.
Almost all the DNA spots with different effects showed up in many psychiatric conditions within the same genetic families. This means that, at the level of common genetic variants, mental health conditions in the same group looked very similar.
These findings showed that traditional distinctions like schizophrenia versus bipolar disorder or major depression versus anxiety do not match up well with common genetic variants. Within each pair, the disorders were almost the same at the genetic level.
But the splits between factor families (psychosis/mania vs internalizing vs addictions) demonstrated clear genetic differentiation.
Contrastingly, the authors observed that significantly greater groupings, such as addictions versus internalizing conditions versus psychosis/mania, were lined up with real genetic variations across their respective families.
Diagnosis and treatment implications
The findings from this study suggest that shared genetic factors, along with their related cell types and pathways, can help us better understand the biology behind how we classify psychiatric disorders.
These essential results could help change how we develop treatments that work across diagnoses, create targeted therapies, and improve ways to predict and assess risk.
Targeting the p-factor could lead to better treatments for many mental illnesses.
Excitatory neuron-related targets may be vital for schizophrenia and bipolar disorders. At the same time, mechanisms involving oligodendrocytes could be more helpful in treating internalizing disorders.
Polygenic scores based on these genetic factors could help measure overall risk for mental illness and more specific risks for psychosis, internalizing, or substance use problems.
This study could have a significant impact on how we assess and treat psychiatric conditions in the future.
Long-term implication
In the future, doctors may stop seeing each mental illness as a separate diagnosis. Instead, they might use a genetic map to treat both the shared causes and unique features of these conditions. However, this will need more research and clinical testing.
Watch the following insightful podcast presenting the complete (step-by-step) breakdown of this study.
Reference
Grotzinger, A.D., Werme, J., Peyrot, W.J. et al. Mapping the genetic landscape across 14 psychiatric disorders. Nature 649, 406–415 (2026). https://doi.org/10.1038/s41586-025-09820-3
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Dr. Khalid Rahman Health Scientist | Scholarly Communicator | Licensed Integrative Medicine Practitioner PhD (Clinical Research) | MSc (Bioinformatics) | MSc (Clinical Research & Regulatory Affairs) | Post Graduate Diploma in Computer Application | Bachelor of Unani Medicine & Surgery
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