Huge genetic study reveals hidden links between psychiatric conditions

Psychiatrists have long relied on diagnostic manuals that regard most mental-health conditions as distinct from one another — depression, for instance, is listed as a separate disorder from anxiety. But a genetic analysis of more than one million people suggests that a host of psychiatric conditions have common biological roots.

The results, published today in Nature¹, reveal that people with seemingly disparate conditions often share many of the same disease-linked genetic variants. The analysis found that 14 major psychiatric disorders cluster into five categories, each characterized by a common set of genetic risk factors. The neurodevelopmental category, for example, includes both attention deficit hyperactivity disorder and autism, which psychiatric handbooks classify as separate conditions.

Many supposedly individual conditions are “ultimately more overlapping than they are distinct, which should offer patients hope”, says study co-author Andrew Grotzinger, a psychiatric geneticist at the University of Colorado Boulder. “You can see the despair on someone’s face [when] you give them five different labels as opposed to one label.”

Fellow travellers

Grotzinger says his team’s work was motivated by the finding that people diagnosed with one mental-health condition are highly likely to be diagnosed with another one. For example, previous research has shown that most people diagnosed with depression have also been diagnosed with a condition called generalized anxiety disorder, and vice versa².

Features of autism can affect age of diagnosis — and so can genes

To learn whether there is a biological explanation for these correlations, Grotzinger and his colleagues aggregated genomic data from more than one million people with psychiatric conditions and from millions of healthy controls.

The researchers found that the 14 mental-health conditions they studied generally fall into five distinct buckets, each with its own genetic profile. There’s a schizophrenia/bipolar disorder category; an ‘internalizing’ category that includes depression, anxiety and post-traumatic stress disorder; a neurodevelopmental category; and a compulsive category that includes obsessive-compulsive disorder and anorexia.

A final category includes substance-use disorders such as alcohol-use disorder and nicotine dependence. People whose genetic profile corresponds to a given bucket are at elevated risk of any of the conditions in that bucket. Other genetic and environmental triggers also affect risk.

Risk sharing

The team then worked backwards from the categories that they had identified and found 238 specific genomic regions that are associated with at least one of these shared categories. For example, the researchers found that one region on chromosome 11 raised genetic risk for eight separate disorders, because the region codes for genes linked to dopamine signalling.

Brain-cell growth keeps mood disorders at bay