An international team of researchers has found that many psychiatric disorders share a common and specific set of gene variants.
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Researchers from Massachusetts General Hospital (MGH) and the Psychiatric Genomics Consortium identified more than 100 genetic variants that contribute to the development of more than one mental health condition.
Identification of the multi-purpose gene variants could provide new clues in the prevention and treatment of psychiatric disorders.
Understanding how specific genetic variations may contribute to a broad spectrum of illnesses can tell us something about the degree to which these disorders may have a shared biology.”
Senior author, Jordan Smoller
An important step towards improving diagnosis and treatment
A gene is a specific sequence of nucleotides along a segment of DNA and any change in that sequence produces a gene variant or mutation that can affect the risk of disease. Many mutations affect the risk for certain psychiatric disorders, but such variants are often “pleiotropic,” meaning they have many different affects.
Smoller says that identifying which variants influence the risk for more than one psychiatric disorder is an important step towards improving the diagnosis and treatment of these conditions.
As reported in the journal Cell, the team performed a genome-wide association study of data available for 232,964 people diagnosed with at least one of eight common psychiatric disorders and 494,162 healthy controls. The eight psychiatric disorders were anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome.
Meta-analysis across these eight disorders identified 109 gene variants that were associated with at least two psychiatric disorders, including 23 variants that had pleiotropic effects on four or more disorders and 11 that had antagonistic effects on multiple disorders.
Dividing the disorders into three genetically-related groups
With certain disorders sharing many variants, the researchers were able to divide them into three groups of genetically-related conditions: those characterized by compulsive behaviors (anorexia nervosa, obsessive-compulsive disorder and, to a lesser extent, Tourette syndrome); mood and psychotic disorders (bipolar disorder, major depression and schizophrenia) and early-onset neurodevelopmental disorders (autism spectrum disorder, ADHD and Tourette syndrome).
“These findings have important implications for psychiatric nosology, drug development, and risk prediction,” writes the team.
The study also found that the pleiotropic variants were located within genes that start to show increased expression in the second trimester of pregnancy and play important roles in neurodevelopmental processes.
Lead author, Phil Lee, says that knowing which gene variants increase the risk for multiple psychiatric disorders provides new clues about the biological pathways that contribute to mental illness.
Learning how disorders are related at a biological level may inform how we classify and diagnose mental health conditions.”
Lead author, Phil Lee
Smoller says the findings could also provide important clues for the prevention and treatment of psychiatric disorders. “To the extent that these genes may have broad effects, they could be potential targets for developing new treatments that might benefit multiple conditions,” he concludes.
Cross-Disorder Group of the Psychiatric Genomics Consortium (2019). Cell. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. DOI: https://doi.org/10.1016/j.cell.2019.11.020