Worldwide genetics study could unlock new treatments for depression

The research, published in Nature Genetics, found more than 50 new genetic loci and 205 novel gene associations with depression in the first big study of the genetics of major depression in study participants of diverse ancestry groups from across the globe. The study also showcases potential for drug repurposing as well as new targets for drugs to treat depression.

Depression is very common, yet how it develops is still poorly understood. Genetic research using big data offers new avenues to understand the disease. It can also help find new drug targets. However, so far research has focussed on people of European ancestry. That is a major shortcoming, especially for such a complex condition as depression. 

This work was a major collaborative effort, involving 21 study cohorts from several countries and included nearly one million participants of African, East Asian, South Asian, and Hispanic/Latin American descent. 

This study made major advances prioritising the genes that are involved in the disease and showcase some genes with potential implications for drug development, such as NDUFAF3. The protein NDUFAF3 encodes is targeted by metformin, the first-line drug for treating type 2 diabetes. 

Surprisingly the researchers found less overlap in the genetic hits for depression across ancestry groups than expected (about 30%). This is less overlap than we found for other traits and diseases.

Therefore, it is even more important to study depression in diverse samples because some of the findings might be ancestry specific.

The work was led by UCL researchers, including Professor Karoline Kuchenbaecker, Dr Xiangrui Meng, Georgina Navoly, PhD researcher and Dr Olga Giannakopoulou. 

Professor Karoline Kuchenbaecker, Professor of Genetic Epidemiology in UCL’s Division of Psychiatry, said: “Here we show beyond doubt that our understanding of such complex diseases as depression will remain incomplete until we overcome the Eurocentric bias in genetics research and look for causes in diverse people across the world.”

The cohorts and major collaborative consortia involved in the study, included the Psychiatric Genomics Consortium-Major Depressive Disorder Working Group, China Kadoorie Biobank Collaborative Group, the 23andMe Research Team, Genes and Health Research Team, and BioBank Japan Project research groups. 

This is a first stage discovery effort so more work will be needed to confirm these new targets but finding them in the first place is a huge challenge, especially for a disorder where new medications are so urgently needed. 

• Research paper in Nature Genetics
• Professor Karoline Kuchenbaecker’s academic profile
• UCL Psychiatry
• UCL Division of Biosciences
• UCL Faculty of Brain Sciences