Psychiatric disorders such as schizophrenia and bipolar disorder often run in families.
In a recent study, researchers explored the genetic connections between these and other disorders of the brain at a scale far beyond previous work.
They found that psychiatric disorders share many genetic variants, while neurological disorders (such as Parkinson’s or Alzheimer’s) appear more distinct.
The study takes the broadest look yet at how genetic variation relates to brain disorders.
The findings indicate that psychiatric disorders likely have important similarities at a molecular level, which current diagnostic categories do not reflect.
Exploring these biological connections is challenging. The brain is a tricky organ to study directly, difficult to scan in detail or ethically biopsy.
And, because brain disorders often co-occur, it’s hard to untangle when one might be affecting the development of another.
To examine the biological overlap between these disorders, researchers must rely on genetics.
For the current study, international consortia pooled their data to examine the genetic patterns across 25 psychiatric and neurological diseases.
Because each genetic variant only contributes a tiny percentage of the risk for developing a given disorder, the analyses required huge sample sizes to separate reliable signals from noise.
The researchers measured the amount of genetic overlap across the disorders using genome-wide association studies (GWAS) of 265,218 patients and 784,643 controls.
They also examined the relationships between brain disorders and 17 physical or cognitive measures, such as years of education, from 1,191,588 individuals.
The dataset ultimately included all GWAS consortia studying common brain disorders that the team could identify with sufficient sample sizes.
The final results indicated widespread genetic overlap across different types of psychiatric disorders, particularly between attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder, and schizophrenia.
The data also indicated a strong overlap between anorexia nervosa and obsessive-compulsive disorder (OCD), as well as between OCD and Tourette syndrome.
In contrast, neurological disorders such as Parkinson’s and multiple sclerosis appeared more distinct from one another and from the psychiatric disorders — except for a migraine, which was genetically correlated to ADHD, major depressive disorder, and Tourette syndrome.
According to the researchers, the high degree of genetic correlation among the psychiatric disorders suggests that current clinical categories do not accurately reflect the underlying biology.
As a hypothetical example, a single mechanism regulating concentration could drive both inattentive behavior in ADHD and diminished executive function in schizophrenia.
Further exploration of these genetic connections could help define new clinical phenotypes and inform treatment development and selection for patients.
Additionally, within the cognitive measures, the researchers were surprised to find that genetic factors predisposing individuals to certain psychiatric disorders — namely anorexia, autism, bipolar, and OCD — were strongly correlated with factors associated with higher childhood cognitive measures, including more years of education and college attainment.
Neurological disorders, however, particularly Alzheimer’s and stroke, were negatively correlated with those same cognitive measures.
It was also surprising that the genetic factors related to many psychiatric disorders were positively correlated with educational attainment,” says Anttila.
The consortia have made their GWAS data accessible online, either freely available for download or by the application.
The team plans to examine additional traits and genetic variants to explore these patterns further, aiming to discover the relevant mechanisms and pathways that underlie and potentially link these disorders.
The study was led by co-senior authors Benjamin Neale. The team further includes researchers from more than 600 institutions worldwide.
The study is published in Science.
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