Psychiatric Disorders Share Underlying Genetic Patterns
Data from nearly a million people reveal genetic ties between conditions.
Posted Jul 05, 2018
Using an enormous dataset to probe the genetic relationship between various brain disorders, an international team of scientists has discovered evidence of substantial overlap in the genetic underpinnings of different psychiatric conditions. Their results were published in the journal Science.
Such associations have been observed previously, but the massive dataset provides compelling new evidence. Understanding the shared genetics of psychiatric conditions could eventually help clinicians refine diagnostic categories and provide targeted treatments.
“This potentially highlights one of the reasons it has been so difficult to diagnose and treat psychiatric disorders,” says co-author Verneri Anttila, a research fellow at the Broad Institute. “Understanding these connections puts us leaps ahead from where we were on the road to understanding these disorders.”
Identifying the genetic connections between psychiatric conditions has important implications for clinicians, says Tinca Polderman, an assistant professor at the Center for Neurogenomics and Cognitive Research at VU University Amsterdam who was not involved in the study. It’s important that diagnostic categories continue to evolve and that treatments may cross over traditional boundaries. For example, a doctor may consider that a drug used to treat one condition might be helpful for a patient with another condition.
The current project began in 2012. Scientists from around the world collected genetic data for nearly a million people—265,218 patients with brain disorders and 784,643 control subjects. They examined 25 brain disorders, including psychiatric conditions such as anxiety, depression, and schizophrenia as well as neurological disorders such as Alzheimer’s disease, epilepsy, and ischemic stroke.
The researchers found that genetic variants associated with psychiatric disorders were highly correlated, especially among five types of disorders: attention deficit hyperactivity disorder (ADHD), anxiety disorders, major depressive disorder (MDD), bipolar disorder, and schizophrenia. In contrast, the researchers did not find significant overlap between the neurological disorders, suggesting that they may have more distinctive causes. The exception to this trend was migraines, which they found to be correlated with ADHD, MDD, and Tourette syndrome.
“It’s a huge dataset, a little unparalleled, so it’s very useful to have these data and analyses available,” says Jonathan Flint, a professor of psychiatry and biobehavioral sciences at University of California Los Angeles, who was not involved in the study. “The fact that psychiatric disorders don’t cleave along the diagnostic groupings that psychiatrists have used has been known for decades really, so it’s adding some icing to that particular cake.”
The team mined the data to investigate an array of questions. They found that the earlier a psychiatric or neurological disorder emerged, the more heritable it was. This is not necessarily surprising, but it’s still an important connection that hasn’t been illustrated before, Anttila says. They also found that the personality trait neuroticism shared genetic risk factors with nearly every psychiatric disorder and was most highly correlated with MDD and anxiety disorders.
The scientists also explored the relationship between genetic variations linked to brain disorders and those connected to years of education, college attainment, and intelligence. For some neurological disorders (such as Alzheimer's disease) and psychiatric conditions (including ADHD and MDD) the overall genetic correlations with such measures were negative, while for some psychiatric conditions—including autism spectrum disorder and obsessive-compulsive disorder—they were largely positive.
Technical aspects of the study, including a novel method of estimating heritability and the approach used to incorporate covariates, could have distorted the findings, Flint says. For example, the frequency of genetic variants differs by country, and the way the researchers controlled for that difference may have impacted the results, he says. Furthermore, certain trends that the authors observed—such as the high genetic correlation between ADHD and MDD—are contrary to results from past studies in which psychiatric geneticists interviewed all members of families with psychiatric disorders.
“I think there are some technical issues that need to be ironed out,” Flint says. “At this stage, I still think this is exploratory.”
Anttila agrees that controlling for factors like population differences is critical. But the research involved multiple safeguards to reduce bias in the results, and he states that “if we observe results which are this significant, if such errors are present in the data, the ‘true’ results would tend to be more significant than what we’ve reported here, not less.” He also acknowledges there are several differences between the genetic correlations his team found and the trends established in previous studies, and he looks forward to follow-up studies that scrutinize those differences.