Scientists have identified hundreds of new genetic links to depression in the largest and most diverse study of its kind, expanding our understanding beyond predominantly European populations.
The research, published today in Cell, analyzed genetic data from more than 5 million people across 29 countries, uncovering nearly 300 previously unknown genetic connections to depression. Notably, 100 of these new discoveries emerged specifically because researchers included populations of African, East Asian, Hispanic, and South Asian descent – groups historically underrepresented in genetic research.
“There are huge gaps in our understanding of clinical depression that limit opportunities to improve outcomes for those affected,” says Professor Andrew McIntosh from the University of Edinburgh’s Centre for Clinical Brain Sciences, who co-led the study. “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 research represents a significant shift from past genetic studies of depression, which have primarily focused on individuals of European ancestry. This historical bias has raised concerns that treatments developed using genetic approaches might not be equally effective across all ethnicities, potentially worsening existing healthcare disparities.
A Global Effort
The international collaboration involved scientists from every continent, including researchers from South Africa, Brazil, Mexico, the United States, Australia, Taiwan, and China. In total, the team analyzed data from 688,808 individuals with depression and 4.4 million controls, making it the largest genetic study of depression ever conducted.
Professor Cathryn Lewis from King’s College London, who co-led the research, emphasizes the study’s unprecedented scope: “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.”
New Treatment Possibilities
The research mapped genetic variations and provided new insights into how depression affects the brain. The identified genetic variants were linked to neurons across multiple brain regions, particularly areas controlling emotion. This understanding has suggested new therapeutic possibilities.
The study identified existing medications that could potentially be repurposed for depression treatment. Two drugs in particular – pregabalin, currently used for chronic pain, and modafinil, prescribed for narcolepsy – showed promise based on their interaction with the newly identified genetic pathways. However, the researchers caution that clinical trials would be needed before any new treatments could be approved.
Breaking Down Genetic Risk
Each genetic variant identified in the study has a small individual effect on depression risk, but these effects can accumulate. The research team developed more accurate methods for predicting an individual’s risk of depression by accounting for these newly identified variants across different ethnicities.
The findings advance our understanding of the genetic architecture of depression across global populations. By including genetic data from diverse ancestries, the study has helped ensure that future genetic research and treatments can benefit people of all ethnic backgrounds more equitably.
The research was funded by the NIH, Wellcome, and the National Institute for Health and Care Research Maudsley Biomedical Research Centre, marking a significant international investment in mental health research.
This comprehensive study advances our understanding of depression’s biological foundations while setting a new standard for inclusive genetic research that could help reduce healthcare disparities worldwide.