Global Genetic Insights into 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.
The world’s largest and most diverse genetic study ever into major depression has revealed nearly 300 previously unknown genetic links to the condition, experts say.

100 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.

Addressing Previous Gaps in Depression Research

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.

Measuring the Cumulative Effects of Gene Variants

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.

Broad International Collaboration and Data Analysis

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.
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.

Linking Genetic Variants to Brain Function

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.

Potential for Drug Repurposing

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

Study Funding and Publication

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
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.

Expert Perspectives on Future Directions

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.”

Original Publication
Authors: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Lead contact: Andrew M. McIntosh
Correspondence: Andrew M. McIntosh (andrew.mcintosh@ed.ac.uk) or Cathryn M. Lewis (cathryn.lewis@kcl.ac.uk)
Journal: Cell
Article Title:Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies
Article Publication Date: 14 January 2025
DOI: 10.1016/j.cell.2024.12.002

Media Contact
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University of Edinburgh
Email ID: jess.conway@ed.ac.uk
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Source: EurekAlert!