5 genetic 'signatures' underpin a range of psychiatric conditions

The largest genetic analysis of psychiatric disorders to date shows that most relevant genetic variants are linked to multiple mental health conditions rather than just one.

The study found that 14 psychiatric disorders can be classified into five major groups, depending on the genetic variants associated with them. For instance, the findings group together anorexia nervosa, obsessive-compulsive disorder (OCD) and Tourette's syndrome according to their shared genetic profile.

The findings, published Dec. 10 in the journal Nature, suggest that disorders within the same group may stem from shared biological mechanisms. An understanding of these common pathways could help scientists develop treatments that work across multiple mental health conditions, the team said.

Chunyu Liu, a professor of psychiatry and behavioral sciences at SUNY Upstate Medical University who was not involved in the study, said the findings make sense based on existing research.

"Even before seeing the results, this is generally expected," Liu told Live Science in an email. "The shared genetics between schizophrenia and bipolar disorder pointed us in this direction [as a field]."

He agrees with the study authors' conclusion that shared genetics point to shared biological mechanisms. However, Liu noted that the study does not explain why clinical symptoms vary so widely between these disorders, even when the underlying genetics overlap.

"It is an important paper, but still a small step toward understanding the disorders," he said.

Genes aren't the whole story

The study showed that many of the genetic variants linked to psychiatric disorders are also linked to other traits, including intelligence; sleep problems like insomnia; personality; social behaviors like aggression; and socioeconomic status.

"Not all of these links are negative," Abdel Abdellaoui, a geneticist at the University of Amsterdam who was not involved in the study, wrote in a commentary article for Nature. For example, the genetic overlap between schizophrenia and bipolar disorder is also associated with traits that can support academic success, such as creativity and persistence.

This nuance matters because embryos used for in vitro fertilization (IVF) are sometimes screened for psychiatric risk factors, which are measured via the embryo's genetics. Parents-to-be then have the option to select embryos with lower "risk scores" for psychiatric disorders. But this choice isn't necessarily clear-cut, Abdellaoui argued. Carrying certain genetic traits doesn't guarantee a disorder will emerge, and the same genes can influence positive traits, such as creativity or resilience, he noted.

Abdellaoui said psychiatric disorders often appear at the extreme ends of a natural range of genetic variation, especially when combined with certain life experiences. In other words, a person can have a genetic predisposition for a given disorder but not ultimately develop it unless they encounter certain adverse events, whether trauma or environmental hazards.

"This should reframe mental illness not as defective biology, but as the unfortunate intersection of natural variation and environmental stress," he said.

The five groupings

To study which genetic variants are unique to each disorder and which are shared across disorders, Andrew Grotzinger, an assistant professor at the Institute for Behavior Genetics at the University of Colorado Boulder and his colleagues analyzed genetic information from more than 1 million people who primarily had European ancestry.

Disorders that share many genetic variants were dubbed "genetically correlated." Using these correlations, the scientists found that the 14 disorders fell into five genomic factors:

Five genomic factors

• Compulsive: Anorexia, OCD, Tourette's
• Neurodevelopmental: Autism, ADHD
• Internalizing: Depression, PTSD, anxiety
• Substance use: Alcohol, cannabis, nicotine and opioid dependence
• Schizophrenia-bipolar

Each genetic factor showed a unique biological pattern, in terms of how the associated genes behave in the brain. For example, genes linked to the schizophrenia-bipolar factor are strongly active in excitatory neurons, which push other neurons to activate, and in brain areas involved in interpreting reality.

Genes linked to the internalizing factor are associated with glia, the brain's support cells. Glia serve as immune protection and maintain connections between neurons, among other roles. This implies that these disorders may relate more to these support cells than to neurons, Abdellaoui said.

The substance-use factor included gene variants that encode the enzyme responsible for breaking down alcohol, and others that encode the receptors that respond to nicotine.

Liu cautioned that these genetic links to psychological disorders should be interpreted carefully. "Genes or biological pathways statistically associated with a disorder should not be interpreted as causal without additional evidence supporting a direct mechanistic role," he said. In short, correlation does not imply causation.

"There are multiple alternative explanations for why a gene is associated with a disorder," he said, "or why two disorders exhibit overlapping genetic signals."