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Large Study Uncovers Genetic Connections Between Numerous Psychiatric Disorders

NEW YORK (GenomeWeb) – Psychiatric disorders share a genetic overlap with each other that neurological disorders do not, a new study has found.

Researchers from the Brainstorm Consortium combined genome-wide association data on more than 265,000 individuals with 25 different psychiatric or neurological disorders to examine their genetic overlap. People with different brain disorders can share similar symptoms, which could suggest a shared biological etiology.

The consortium researchers also folded in data from more than 1 million other individuals to investigate the relationship between brain disorders and 17 other phenotypes such as educational attainment, neuroticism, and coronary artery disease.

As the researchers reported today in Science, they found that common risk variants were shared among many psychiatric disorders — including between attention-deficient/hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia — but that neurological disorders were more distinct from one another. According to the researchers, this indicates that the clinical boundaries between psychiatric disorders might not reflect the underlying biology of the conditions.

"This work is starting to reshape how we think about disorders of the brain," co-­senior author Ben Neale from the Broad Institute said in a statement. "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."

The consortium collected GWAS meta-analysis summary statistics for 25 brain disorders to create a cohort of 265,218 cases and 784,643 controls of European ancestry. The researchers used a linkage disequilibrium score regression approach they developed to calculate heritability estimates and correlations.

For most of the disorders, the heritability estimates the researchers developed were broadly similar to those reported by smaller studies. The estimates from this study were typically slightly lower than previous ones but the researchers largely attributed that to the increased diagnostic heterogeneity of a larger cohort and ascertainment error.

Neale and his colleagues noted widespread genetic sharing among psychiatric disorders. For instance, they uncovered significant genetic correlations between schizophrenia and most other psychiatric disorders as well as between major depressive disorder and every other disorder examined. In particular, they found that schizophrenia, bipolar disorder, anxiety disorders, major depressive disorder, and ADHD were each highly correlated to the others. Likewise, the researchers noted a genetic overlap between anorexia nervosa, OCD, and schizophrenia.

The association between schizophrenia and ADHD, for instance, could reflect the disorders' shared effects on executive function, the researchers noted.

The neurological disorders, by contrast, exhibited more limited sharing, they reported. This suggests that there may be more distinct etiology between, for example, Parkinson's disease, Alzheimer's disease, and epilepsy, or greater diagnostic specificity, they said.

There were also limited genetic correlations between the neurological and psychiatric disorders, according to the researchers. Only migraine appeared to have some genetic overlap with ADHD, Tourette's syndrome, and major depressive disorder.

The consortium also collected GWAS meta-analysis summary statistics for 17 other phenotypes, including 13 behavioral-cognitive phenotypes and four other conditions, including Crohn's disease and coronary artery disease. This yielded a cohort of around 1.2 million individuals.

In these individuals, the researchers uncovered a number of significant genetic associations between these phenotypes and brain disorders. They reported, for example, correlations between neuroticism and anorexia nervosa and between BMI and ADHD or major depressive disorder.

The researchers added that further exploration of these connections could help better define clinical phenotypes and point to better treatment approaches.

"The tradition of drawing these sharp lines when patients are diagnosed probably doesn't follow the reality, where mechanisms in the brain might cause overlapping symptoms," Neale said.