Psychiatric Disorders, Unlike Neurological Disorders, Show Overlapping Genetic Risks

June 22, 2018
Psychiatric Disorders, Unlike Neurological Disorders, Show Overlapping Genetic Risks
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Clinical categories for psychiatric disorders may need to be rethought, suggests a new study from the aptly named Brainstorm Consortium, a collaborative effort that accepted input from researchers representing 600 institutions worldwide. By pooling their data on hundreds of thousands of genomes, these researchers found genetic connections among distinct psychiatric disorders. In contrast, the researchers observed that neurological disorders, such as Parkinson’s and Alzheimer’s, possess relatively little genetic overlap.

Detailed findings from the study appeared June 19 in the journal Science, in an article entitled “Analysis of Shared Heritability in Common Disorders of the Brain.” The article describes how the Brainstorm Consortium quantified the genetic sharing of 25 brain disorders from genome-wide association studies (GWASs) of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals.

“Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia,” the articles authors wrote. “By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome.”

The study was led by co-senior authors Ben Neale, Ph.D., director of population genetics at Broad Institute of MIT and Harvard, and Aiden Corvin, Ph.D., professor at Trinity College Dublin, with first author Verneri Anttila, Ph.D., a postdoctoral research fellow in Neale's lab.

"This work is starting to reshape how we think about disorders of the brain," noted Neale. "If we can uncover the genetic influences and patterns of overlap between different disorders, then we might be able to better understand the root causes of these conditions—and potentially identify specific mechanisms appropriate for tailored treatments."

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, the researchers pooled their data to uncover genetic patterns that might have escaped notice in less data-rich studies. Because each genetic variant only contributes a tiny percentage of the risk for developing a given disorder, huge sample sizes are needed to separate reliable signals from noise.

"We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine,” the Science article continued. “We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer’s disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life.”

"We were surprised that genetic factors of some neurological diseases, normally associated with the elderly, were negatively linked to genetic factors affecting early cognitive measures,” Anttila remarked. “It was also surprising that the genetic factors related to many psychiatric disorders were positively correlated with educational attainment. We'll need more work and even larger sample sizes to understand these connections."

In their conclusions, the researchers emphasized that the high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. “The high degree of genetic correlation among many of the psychiatric disorders,” the researchers asserted, “suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics.”