Mental and cardiometabolic disorders are clearly associated, since people with mental disorders such as depression, bipolar and attention-deficit/hyperactivity disorder (ADHD) more often develop cardiometabolic disorders than the rest of the population. Now researchers have quantified the relative genetic and environmental contributions underlying this comorbidity.
Having a mental disorder such as ADHD, bipolar disorder, depression or schizophrenia is associated with an increased risk of cardiometabolic disorder and premature death.
Depending on the diagnosis, individuals with a mental disorder generally have 5 to 15 years less life expectancy.
However, the big question has long been how much of this association results from the genetic factors known to overlap between mental and cardiometabolic disorders and how much results from the environment.
Many people with mental disorders have unhealthy lifestyles or take medication, thereby increasing their risk of developing cardiometabolic disorders and premature death.
Now a new study with data spanning 17 million individuals in Denmark and Sweden has quantified the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders.
“This may strongly affect how we approach treating people with both mental and cardiometabolic disorders. If genes largely cause the association, they may need genetic counselling, but if environmental factors cause most of the association, doctors need to use other tools to curb unhealthy lifestyles or prescribe other drugs,” explains a researcher behind the study, Joeri Meijsen, Postdoctoral Fellow, Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Copenhagen University Hospital, Roskilde, Denmark.
The research has been published in Nature Communications.
Asking three questions
The researchers obtained relevant data on 17 million individuals living in Denmark and Sweden to shed light on what can explain the associations between various mental and cardiometabolic disorders.
Both Denmark and Sweden have excellent registries available for research, but since neither country has genetically sequenced the entire population, the researchers compared diagnoses between family members to determine the hereditary component in developing both mental and cardiometabolic disorders.
The researchers then examined the risk of a family member of a person with mental or cardiometabolic disorders developing a given disorder compared with the general population.
This enabled the researchers to answer three unique questions.
- How much of the difference between individuals with specific mental disorders is caused by genetic differences?
- How much genetic overlap is there between specific mental disorders and various cardiometabolic disorders, including obesity, diabetes and heart failure?
- How much of the association between mental and cardiometabolic disorders can be explained by genetics versus the environment?
Hereditability component present in all mental disorders
The researchers identified the hereditable component of various mental and cardiometabolic disorders.
The genetic component explains 65% of the difference between a person with and without ADHD versus 55% for schizophrenia, 60% for autism, 35% for anorexia and 30% for depression.
“Everything was as we expected, because this has been investigated before. But it shows that our method of investigating the genetics behind various mental disorders works, even if we do not have direct access to the genetic information for individual patients in the study,” says Joeri Meijsen.
ADHD and cardiometabolic disorders have strong genetic overlap
The researchers found that the genetic overlap differs greatly between mental disorders and cardiometabolic disorders.
For example, ADHD had a relatively large genetic overlap across 14 of the 15 cardiometabolic disorders examined, meaning that up to 50% of the genetic architecture is relevant for both diagnoses.
The researchers found the same result for depression, but schizophrenia had virtually no genetic overlap with the cardiometabolic disorders – only genetic overlap was observed with heart failure.
“This was very surprising. Schizophrenia is the mental disorder that reduces life expectancy the most and has the most comorbid cardiometabolic disorders. We therefore thought that the genetic overlap with cardiometabolic disorders would be greater than we found. Conversely, the considerable overlap between ADHD and the many cardiometabolic disorders was completely as expected,” explains Joeri Meijsen.
Both strong and weak genetic associations
Regarding the third question, the researchers tried to determine how much of the increased risk people with mental disorders have of developing a cardiometabolic disorder can be attributed to genetics and how much to the environment.
Why, for example, do people with ADHD have twice the risk of developing diabetes as individuals without ADHD?
This part of the study, in which the researchers matched the five mental disorders investigated in pairs with seven cardiometabolic disorders, showed that genetics can explain up to 50% of the association between ADHD and affective disorders and the various cardiometabolic disorders.
However, there are many grey areas. For example, the researchers found no evidence that genetics contributes to individuals with autism having an increased risk of developing high blood pressure.
Conversely, the associations between autism and anorexia and various cardiometabolic disorders are driven almost entirely by the environment and have little to do with genetic factors.
“The discovery means that we can now inform doctors who have a patient with a mental disorder and an increased risk of developing a cardiometabolic disorder how much of this increased risk is genetic and how much is caused by the environment. Doctors can make a plan based on this information and, for example, provide genetic counselling if genetics is a dominant cause of the association. If the association almost exclusively results from the environment, the doctor should approach the patient differently,” concludes Joeri Meijsen.
