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.

The study is published in the journal Cell on the 14th of January 2025. Read paper here.

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.

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.

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 wealth of insights from the present study could open new possibilities to develop effective strategies to prevent and treat this disabling condition.
Yuri Milaneschi
Assistant professor of psychiatry and epidemiology at the Department of Psychiatry of Amsterdam UMC

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 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.

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.

About the team

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

Several researchers affiliated with Amsterdam Public Health and Amsterdam Neuroscience were involved in the study: Eco de Geus, Aartjan Beekman, Floris Huider, Rick Jansen, Yuri Milaneschi, Wouter Peyrot, Dorret Boomsma, Jurjen Luykx, Christel Middeldorp, Brenda Penninx and Karin Verweij.

Yuri Milaneschi, who worked on data from the NESDA study for the analyses, said: "With NESDA, we have been involved in the Psychiatric Genomics Consortium since its inception. This collaborative effort grew over the years and enabled us to present, in the current study, the most extensive examination of the genetic basis of depression. This mental disorder remains one of the most difficult challenges for our societies and public health systems. The wealth of insights from the present study could open new possibilities to develop effective strategies to prevent and treat this disabling condition."

Source: psychiatryamsterdam.nl