Global study pinpoints genes for depression across ethnicities

New genetic risk factors for depression have been identified across all major global populations for the first time, allowing scientists to predict risk of depression regardless of ethnicity.

A research team led by Professor Andrew McIntosh and including Generation Scotland’s Dr Mark Adams and Dr Xueyi Shen, and Dr Pippa Thomson of the Institute of Genetics and Cancer, conducted the world’s largest and most diverse genetic study ever into major depression which revealed nearly 300 previously unknown genetic links to the condition. This significant research is the largest of its kind, combining data from 93 studies, including the Generation Scotland study. 

One hundred of the newly discovered genetic variations – small differences in the DNA sequence that makes up a gene – were identified due to the inclusion of people of African, East Asian, Hispanic and South Asian descent.

Previous research into the genetics of depression has focused primarily on populations of European ancestry. Therapies developed using genetic approaches may therefore not be effective in other ethnicities, widening existing health inequalities.

Each single genetic variant has a very small effect on the overall risk of developing depression. If a person has multiple variants, these small effects can add up, increasing their risk.

The research team were able to more accurately predict an individual’s risk of depression by taking into account the newly identified variants.

The international team of scientists, led by the University of Edinburgh and King’s College London, looked at anonymised genetic data from more than five million people in 29 countries worldwide. One in four individuals included in the study were from non-European ancestries.

This is the largest and most inclusive genetic study of a psychiatric disorder to date, using data from across the globe on over half a million people who are affected by depression. Our findings have identified much more specific brain regions implicated in the biology of depression, and the challenge now is to determine which of these insights can be translated into better treatments.

Dr Mark Adams Institute for Neuroscience and Cardiovascular Research

Researchers identified a total of 700 variations in the genetic code of individuals linked to the development of depression, almost half of which had never been associated with the condition before, implicating 308 specific genes.

The identified genetic variants were linked to neurons - a type of brain cell important in the transmission and interpretation of information - across multiple brain regions, including areas which control emotion.

The findings offer new insight into depression’s impact on the brain and present possible new targets for treatment.

The research team highlights the existing drugs pregabalin and modafinil – used to treat chronic pain and the sleeping condition narcolepsy, respectively – which could potentially be repurposed for the treatment of depression, based on the study findings. However, the team cautions that further studies and clinical trials are needed to explore the potential of the drugs in patients with depression.

The study, funded by NIH, Wellcome and the National Institute for Health and Care Research Maudsley Biomedical Research Centre, is published in the journal Cell and an article entitled 'Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies'.

The research team from the Psychiatric Genomics Consortium involved scientists from all continents, including studies from South Africa, Brazil, Mexico, the USA, Australia, Taiwan and China, as well as those from Europe.

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

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.” 

Dr Pippa Thomson, co-author from the Institute of Genetics and Cancer said "It is wonderful to see The Generation Scotland project continuing to contribute to worldwide efforts to understand the biological basis of depression. Such research holds the promise of identifying treatments that reduce the impact of this terrible condition on individuals, families and the wider community. ”

Further information on Generation Scotland

Generation Scotland serves as a vital bridge between volunteers and top scientists, driving efforts to improve the understanding, prevention and treatment of various health conditions. With over 40,000 volunteers, the study focuses on topics including mental health, loneliness, the impacts of lockdown, cancer, dementia, diabetes, reproductive health and many more. All of this research is made possible with the data provided by volunteers. To continue advancing health research, Generation Scotland is currently recruiting participants, and is open to anyone aged 12+ in Scotland, aiming to represent the country’s full diversity.

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