Depression risk identified in largest and most diverse genetic study ever

New research has revealed nearly 300 previously unknown genetic links to depression, in the world’s largest and most diverse genetic study into the condition ever.

One hundred of the newly discovered genetic variations were found due to the inclusion of people of African, East Asian, Hispanic and South Asian descent, because previous research has focussed on white European participants.

Existing therapies that were developed from genetic research into depression may therefore be ineffective in non-white people, widening existing health inequalities.

The authors say the findings, published in the journal Cell, will allow scientists to predict risk of major depression regardless of ethnicity and may help to develop more effective therapies for the condition.

“Genetic research has made huge advances in recent years, but there is a risk that not everyone will benefit when research findings are largely based on study participants of European descent,” said joint senior author Professor Karoline Kuchenbaecker, UCL Genetics Institute and UCL Psychiatry.

“Studies like ours that include data from diverse groups of people are vital to ensure that we are not missing a major piece of the puzzle.”

The research team looked at anonymised genetic data from more than five million people in 29 countries across the globe. One in four individuals included in the study were from non-European descent.

Researchers identified 700 variations in the genetic code of individuals linked to depression, 308 of which had never been associated with the condition. They noted that each genetic variant has a small impact on the risk of developing depression, but having multiple variants can add up and increase an individual’s risk.

The identified variants were linked to neurons (nerve cells), across multiple brain regions, including areas which control emotion.

The findings offer new insight into depression’s effect on the brain and offer possible new targets for treatment, experts say.

“There are huge gaps in our understanding of clinical depression that limit opportunities to improve outcomes for those affected,” said Professor Andrew McIntosh, study co-lead, from the University of Edinburgh’s Centre for Clinical Brain Sciences.

“Larger and more globally representative studies are vital to provide the insights needed to develop new and better therapies, and prevent illness in those at higher risk of developing the condition.”

The team highlighted that existing drugs pregabalin and modafinil – currently used to treat chronic pain and the narcolepsy, respectively – could potentially be repurposed for the treatment of depression, based on the study findings.

However, the team caution that further studies and clinical trials are needed to explore the potential of the drugs in patients with depression.

Professor Cathryn Lewis, study co-lead, from the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, said: “Depression is a highly prevalent disorder and we still have a lot to learn about its biological underpinnings. Our study identifies hundreds of additional genetic variants that play a role in depression.

“These findings show depression is highly polygenic and open up downstream pathways to translate these findings into better care for people with depression.”