Scientists find hundreds more genetic risk factors for depression | Depression

A global study has identified 300 previously unknown genetic risk factors for depression because it included a much wider population sample.

According to the World Health Organization, 3.8% of the population has depression at any one time, affecting about 280 million people.

While a range of factors including adverse life events, physical ill health and stress can increase the risk of developing depression, it also has a genetic component.

An international team of researchers, led by the University of Edinburgh and King’s College London, studied anonymised genetic data from more than 5 million people in 29 countries, with one in four from non-European ancestries.

Previous research into the genetics of depression has primarily involved white, richer populations, neglecting most of the world. But by including a more diverse sample, the authors were able to identify new risk factors.

The study, published in the journal Cell, found 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.

These small changes in DNA were linked to neurons in multiple brain regions, including areas that control emotion.

In all, 100 of the previously unknown genetic differences were specifically identified because people of African, east Asian, Hispanic and south Asian descent were included in the study.

While each genetic risk factor for depression is very small, the cumulative impact for individuals with multiple DNA variants, can increase their risk, the study found.

The authors believe the findings will allow scientists to predict the risk of depression more accurately, regardless of ethnicity, and to develop more diverse treatment options, helping to reduce health inequalities.

The study calculated that 308 genes were associated with higher risk of depression. The researchers then examined more than 1,600 medications to see if they had an impact on those genes. In addition to antidepressants, the study identified that Pregabalin, used for chronic pain, and Modafinil, used for narcolepsy, also had an effect on these genes and could therefore potentially be used to treat depression. Further studies and clinical trials would be needed to explore the potential of these drugs in patients with depression, the authors said.

Prof Andrew McIntosh, who is one of the lead authors on the study and 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.”

Responding to the findings, Dr David Crepaz-Keay, the head of research and applied learning at the Mental Health Foundation, said that the study’s diverse gene pool was “a significant step forward” but that genetic risk factors should not be used as a definitive guide to treatment.

“While research like this can help shape measures for those at higher genetic risk, the prevention of depression must focus on addressing the broader issues in society that impact mental health to a much greater extent, such as experiences of poverty or racism,” he added.

Dr Jana de Villiers, a spokesperson for the Royal College of Psychiatrists, said: “We welcome this research into the genetic variants that can make people more susceptible to depression, and its diversity in terms of global representation makes it particularly noteworthy. By improving our understanding of genetic risk factors and the causes of mental illness, we may be able to develop better treatment methods.

“We will continue to support ongoing efforts to prevent mental illness and improve outcomes for those affected by depression.”