Jordan W. Smoller
Researchers have identified eight psychiatric disorders that share a common genetic structure, according to study results published in Cell.
“This study provides further evidence that genetic influences on psychiatric disorders transcend the boundaries of our clinical categories,” Jordan W. Smoller, MD, ScD, director of Massachusetts General Hospital’s Psychiatric and Neurodevelopmental Genetics Unit, told Healio Psychiatry. “Our current system of diagnosis is based largely on groups of symptoms rather than causes. Studies like this one can help inform efforts to move towards a system based on underlying causes.”
Smoller and colleagues, who comprised several consortiums for a total of more than 600 scientists, used genome-wide association analyses of 232,964 individuals diagnosed with one of eight psychiatric disorders — anorexia nervosa, ADHD, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia and Tourette syndrome. They also analyzed genetic data of 494,162 healthy controls.
The researchers reported that genetic correlation analysis revealed a meaningful structure within the eight disorders, and it identified three groups of inter-related disorders. Using meta-analysis across these disorders, they detected 109 loci associated with at least two psychiatric disorders. Shared variants allowed the researchers to classify conditions into three groups by their related genetics — those characterized by compulsive behaviors, including anorexia nervosa, OCD and, to a lesser extent, Tourette syndrome; mood and psychotic disorders including bipolar disorder, major depression and schizophrenia; and early-onset neurodevelopmental disorders including ASD, ADHD and Tourette syndrome.
Further, they noted that genes associated with multiple disorders exhibit increased expression beginning in the second trimester of pregnancy. These genes appear to impact brain development, they wrote. The findings also revealed that certain gene variants had especially widespread influence on the risk for multiple psychiatric disorders.
“By pointing to pathways that are shared across disorders, this work may inform the development of therapies by understanding the spectrum of behaviors they are likely to target,” Smoller said. “This really drives home how widespread pleiotropy is in psychiatric genetics.” – by Joe Gramigna
Disclosures: Smoller reports unpaid membership of the Bipolar/Depression Research Community Advisory Panel and of 23andMe. Please see the study for all other authors’ relevant financial disclosures.