A University of Leicester study has contributed to the world’s largest and most diverse genetic study ever into major depression, helping to reveal nearly 300 previously unknown genetic links to the condition.
The study identified genetic risk factors for depression across all major global populations for the first time, allowing scientists to predict risk of depression regardless of ethnicity.
An 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. 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.
Among those contributing to the data was the University of Leicester’s EXCEED study – Extended Cohort for E-health, Environment and DNA – which looks at the causes of long-term health conditions by collecting information about genes and lifestyle from those living across Leicester, Leicestershire and Rutland. Data from around 2,600 EXCEED volunteers fed into this global research 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, the study found.
Previous research into the genetics of depression has focused primarily on white populations that originally descended from people living in Europe. Therapies developed using genetic approaches may therefore not be effective in other ethnicities, widening existing health inequalities.
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. 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 identified genetic variants were linked to neurons – a type of brain cell – 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, experts say.
However, the team caution 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: https://www.cell.com/cell/fulltext/S0092-8674(24)01415-6.
Dr Catherine John, Scientific Director of EXCEED and co-author of the study, said: “We’re delighted that EXCEED has been able to contribute to this landmark study, which will help scientists to better understand the causes of depression, how it can best be treated and even prevented in the first place. It’s thought that around 1 in every 6 adults in Leicester, Leicestershire and Rutland have depression or anxiety, so this is a really important area of research for us. We are grateful to all the volunteers who have helped make this possible by taking part in EXCEED, and we hope to reach out communities in Leicester later this year to ask for more volunteers.”
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.”