In a groundbreaking worldwide study led by researchers at University College London (UCL), more than 200 genes associated with depression have been discovered. The study, published in Nature Genetics, examined the genetics of major depression in a diverse range of participants from various ancestry groups, shedding new light on the complexity of the condition.

The research team utilized multiple genetic research methods, including genome-wide association studies and a meta-analysis of previously published data, to analyze genetic information from 21 cohorts spanning different countries. In total, nearly one million study participants were included in the analysis, with representation from African, East Asian, South Asian, and Hispanic/Latin American descent.

Within this comprehensive dataset, the study identified over 50 new genetic loci and 205 novel genes that are linked to depression, marking the largest-scale global investigation of depression genetics to date. These findings represent significant progress in understanding the genetic basis of depression and present potential avenues for drug development and personalized treatment approaches.

One particularly promising discovery from the study is the identification of a gene encoding a protein targeted by a common diabetes drug, metformin. This finding suggests the potential for repurposing existing medications to treat depression. Previous animal studies have also hinted at a connection between metformin and reduced symptoms of depression and anxiety.

While previous research on depression genetics has primarily focused on individuals of European ancestry, this study's inclusion of diverse ancestry groups addresses a critical shortcoming in our understanding of the condition. The research team found that the overlap in genetic findings for depression across different ancestry groups was lower than anticipated, indicating the importance of studying depression in diverse populations to capture ancestry-specific factors.

Lead author Professor Karoline Kuchenbaecker, from UCL Psychiatry and UCL Genetics Institute, emphasized the need to overcome the Eurocentric bias in genetics research to gain a more comprehensive understanding of complex diseases like depression. The study's findings underscore the significance of diverse genetic datasets to ensure the development of effective treatments that benefit individuals of all ancestries.

Although this study represents a crucial first step in identifying new targets for depression treatment, further research is necessary to confirm these findings. Nevertheless, the discoveries made thus far have paved the way for future investigations and hold promise for addressing the urgent need for new medications to alleviate the burden of depression.

The global study's comprehensive exploration of the genetics of major depression has not only revealed previously unrecognized genes associated with depression but has also highlighted the importance of diversity in genetic research. By expanding our knowledge of depression genetics and its varying impacts across ancestry groups, researchers are inching closer to more effective interventions for this pervasive mental health condition.

Reference:
Xiangrui Meng et al, Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference, Nature Genetics (2024). DOI: 10.1038/s41588-023-01596-4