Mental health: Most disorders including bipolar and schizophrenia arise from a set of common genes
People with autism, attention deficit hyperactivity disorder (ADHD), and Tourette syndrome may have different challenges, but these mental disorders arise from a common set of genes.
Many distinct psychiatric diseases share a common genetic structure, according to a new study by scientists from the Massachusetts General Hospital (MGH) and the Psychiatric Genomics Consortium, an international team of investigators.
It shows that there is a common set of genes that increase a person's risk for all three disorders.
Mental disorders are common in the US: Nearly one in five US adults live with a mental illness, according to the National Institute of Mental Health (NIMH). The prevalence was higher among women (22.3%) than men (15.1%).
The new study identifies 109 genetic variants that affect the risk for more than one mental health condition.
Significantly, researchers found evidence that genes associated with a large number of disorders also begin to show increased expression in the second trimester of pregnancy, and appear to play an important role in brain development.
Certain disorders shared many variants, allowing researchers to divide the conditions into three groups of genetically-related conditions, says the analysis published in Cell.
This includes disorders 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).
“Previous studies have shown that there is a sharing of genetic influences among psychiatric disorders, but this study went beyond what's been shown before. For example, we were able to put together genomic data for more than 725,000 individuals across eight different disorders," the study's senior author, Dr. Jordan W. Smoller, tells MEA WorldWide (MEAWW).
Smoller continues, "We found evidence that the disorders clustered into three groups of genetically related disorders: a group related to compulsive behaviors, a group involving mood and psychotic disorders, and a group that predominantly included disorders of development."
“This suggests that genetic influences are telling a different story about how disorders are related than the standard diagnostic classification that we use clinically," Dr. Smoller -- director of MGH's Psychiatric and Neurodevelopmental Genetics Unit and a professor of psychiatry at Harvard Medical School (HMS) tells MEAWW.
According to Dr. Smoller, understanding the genes and pathways involved in psychiatric disorders may also help in developing new treatments.
"This work suggests that targeting certain shared pathways might have effects on multiple conditions," he says.
NIMH estimates show that in 2017, there were 46.6 million adults aged 18 or older in the US living with any mental illness. Further, there were an estimated 11.2 million adults aged 18 or older in the US with a serious mental illness in 2017.
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A gene is made up of segments of DNA. An alteration in the DNA sequence produces a gene variant, which can increase or decrease the risk of disease. Many individual gene variants that affect the risk for specific psychiatric disorders have been identified.
However, genes are often pleiotropic, meaning they produce multiple effects in the body, says the research team. Hence, identifying gene variants that influence the risk for more than one psychiatric disorder is an important step toward improving the diagnosis and treatment of these conditions.
"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 shared biology," says Dr. Smoller.
To identify these multi-purpose gene variants, the researchers used a technique called genome-wide association to analyze genetic data from 494,162 healthy control subjects and 232,964 people diagnosed with at least one of eight common psychiatric disorders.
The study identified several gene variants that had especially widespread influence on the risk for a number of psychiatric disorders, which could prove to be an important finding for the prevention and care of mental disorders.
“We identified 109 specific genetic loci that seemed to be associated with more than one psychiatric disorder. In some cases, individual genetic loci were associated with as many as four or more disorders." Dr. Smoller shares.
"The message seems to be that there is a great deal of 'pleiotropy' when it comes to genetic variants that affect risk for mental illness. When we looked into the biological function of these 'pleiotropic' loci, we found that many of them are in pathways related to brain development," he adds.
He continues: "Interestingly, we also see genetic variants that have opposite effects on different disorders — that is, they may increase the risk for one disorder but reduce the risk for another, underscoring just how complex the genetic basis of psychiatric disorders can be."
According to Dr. Smoller, the work gives a better understanding of how psychiatric disorders arise and how they are related.
"Right now, our diagnostic system is based on collections of symptoms and the consensus of experts. This work and other efforts may help us move toward an understanding of mental health conditions based on their underlying causes, though that will likely be a process that unfolds over time," he points out.
The analysis reveals that certain psychiatric diseases are more similar biologically than their characteristic symptoms indicate.
"Our findings may also help make sense of the fact that many mental health symptoms can be part of different disorders and often don’t neatly fit into a single category."
"Many people may be affected with more than one mental health condition — that may reflect in part this observation that fundamentally, many of these conditions have shared biology,” Dr. Smoller tells MEAWW.