Resume: The study reports an overlap between genetic architecture and comorbid mental health diagnosis. The researchers found that 70% of the genetic signals associated with schizophrenia were also related to bipolar disorder. Anorexia and OCD have a strong shared genetic architecture.
Source: university of colorado
More than half of people diagnosed with a psychiatric disorder will be diagnosed with a second or third in their life. About a third have four or more.
This can make treatment difficult and leave patients feeling unlucky and discouraged.
But a comprehensive new analysis of 11 major psychiatric disorders offers new insight into why comorbidities are the norm, rather than the exception, when it comes to mental illness.
The study, published this week in the journal Nature Genetics, found that while there is no one gene or set of genes underlying risk for all of them, subsets of disorders, including bipolar disorder and schizophrenia; anorexia nervosa and obsessive-compulsive disorder; and major depression and anxiety share a common genetic architecture.
“Our findings confirm that high comorbidity in some disorders partly reflects overlapping pathways of genetic risk,” said lead author Andrew Grotzinger, an assistant professor in the Department of Psychology and Neuroscience.
Ultimately, the finding could open the door to treatments that address multiple psychiatric disorders at once and help reshape the way diagnoses are made, he said.
“If you had a cold, you wouldn’t want to be diagnosed with a cough disorder, a sneezing disorder, and a joint pain disorder,” Grotzinger said.
“This study is a stepping stone toward creating a diagnostic manual that better maps what’s really going on biologically.”
How the study worked
For the study, Grotzinger and colleagues from the University of Texas at Austin, the Vrije Universiteit Amsterdam, and other collaborating institutions analyzed publicly available genome-wide association (GWAS) data from hundreds of thousands of people who submitted genetic material to datasets. on a large scale, such as the UK Biobank and the Psychiatric Genomics Consortium.
They analyzed genes associated with 11 disorders, including: schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, anorexia nervosa, obsessive-compulsive disorder, Tourette’s syndrome, post-traumatic stress disorder, problematic alcohol use, ADHD and autism.
Additionally, they analyzed data collected through wearable motion-tracking devices and survey data documenting physical and behavioral traits.
They then applied new statistical genetic methods to identify common patterns across disorders.
Linked Diagnostics
They found that 70% of the genetic signal associated with schizophrenia is also associated with bipolar disorder. That finding was surprising since, under current diagnostic guidelines, doctors typically won’t diagnose an individual with both.
They also found that anorexia nervosa and obsessive-compulsive disorder have a strong shared genetic architecture, and that people with a genetic predisposition to have a smaller body type or a low BMI (body mass index) also tend to have a genetic predisposition to these disorders. .
Unsurprisingly, since the two diagnoses often go together, the study found a large genetic overlap between anxiety disorder and major depressive disorder.
Analyzing the accelerometer data, the researchers found that disorders that tend to cluster together also tend to share genes that influence how and when we move during the day.
For example, those with internalizing disorders, such as anxiety and depression, tend to have a genetic architecture associated with little movement throughout the day.
Compulsive disorders (OCD, anorexia) tend to correlate with genes associated with increased movement throughout the day, and psychotic disorders (schizophrenia and bipolar disorder) tend to correlate genetically with excessive movement in the early morning .
“When you think about it, it makes sense,” Grotzinger said, noting that depressed people often present with fatigue or low energy, while people with compulsive disorders may have difficulty sitting still.
In all, the study identifies 152 genetic variants shared across multiple disorders, including those already known to influence certain types of brain cells.
For example, genetic variants that influence excitatory and GABAergic brain neurons, which are involved in critical signaling pathways in the brain, appear to underlie the strong genetic signal that is shared between schizophrenia and bipolar disorder.
Whats Next
While much more needs to be done to determine exactly what the identified genes do, Grotzinger sees the research as a first step toward developing therapies that can address multiple disorders with a single treatment.
“People today are more likely to be prescribed multiple medications intended to treat multiple diagnoses, and in some cases those medications can have side effects,” he said.
See also
“By identifying what is shared in these problems, hopefully we can find ways to approach them in a different way that doesn’t require four separate pills or four separate psychotherapy interventions.”
In the meantime, simply understanding the genetics underlying their disorders may bring comfort to some.
“It’s important for people to know that they’ve not just had one terrible roll of the dice in life, that they’re not dealing with multiple different problems, but a set of risk factors that affect them all.”
About this research news in genetics and mental health
Author: press office
Source: university of colorado
Contact: Press Office – University of Colorado
Image: The image is in the public domain.
original research: Open access.
“Genetic architecture of 11 major psychiatric disorders at the biobehavioral, functional genomic, and molecular genetic analysis levels” by Andrew D. Grotzinger et al. Nature Genetics
Resume
Genetic architecture of 11 major psychiatric disorders at the biobehavioral, functional genomic, and molecular genetic analysis levels
We interrogated the joint genetic architecture of 11 major psychiatric disorders at the level of biobehavioral, functional genomic, and molecular genetic analysis.
We identified four broad factors (neurodevelopmental, compulsive, psychotic, and internalizing) that underlie genetic correlations between disorders and tested whether these factors adequately explain their genetic correlations with biobehavioral traits.
We present the stratified genomic structural equations model, which we use to identify sets of genes that contribute disproportionately to shared genetic risk. This includes genes intolerant to variants that truncate proteins expressed in excitatory and GABAergic brain cells that are enriched for genetic overlap in disorders with psychotic features.
Multivariate association analyzes detect 152 (20 new) independent loci that act on individual factors and identify nine loci that act heterogeneously on disorders within a factor.
Despite moderate to high genetic correlations across all 11 disorders, we found little utility for a single dimension of genetic risk in psychiatric disorders, either at the level of biobehavioral correlates or at the level of individual variants.
