More than 200 genes linked to depression were recently identified in a worldwide study led by UCL researchers. Research has discovered more than 50 new genetic loci (a locus is a specific location on a chromosome) and 205 new genes associated with depressive disorder in the first large-scale global study of the genetics of major depression in participants of different origin groups.
The results of the study were published in Nature Genetics.
Depression: Here's how identified genes can help develop new treatments
The study also shows the potential for drug repurposing, as one of the identified genes encodes a protein targeted by a common diabetes drug, also indicating new targets for drugs that could be developed to treat depression.
Depression is very common, but how it develops is still poorly understood. Genetic research using big data offers new avenues for understanding the disease and has discovered dozens of genes associated with the disease, each of which individually confers only a small increase in risk.
It can also help find new drug targets, but research so far has focused mostly on people of European descent, which researchers say is a major gap, especially for a complex condition like depression.
The new study involved multiple genetic research methods, including genome-wide association studies, a meta-analysis of previously published data, and a transcriptome-wide association study.
The international research team examined genetic data from 21 study cohorts from multiple countries and included nearly one million study participants of African, East Asian, South Asian, and Hispanic/Latin American descent, including 88,316 people with major depression.
The study has made important progress in identifying genes linked to depression risk, both by newly identified links and by strengthening previous evidence, and showcases some genes with potential implications for drug development, such as NDUFAF3.
The protein encoded by NDUFAF3 has previously been implicated in mood instability and is targeted by metformin, the first-line drug for the treatment of type 2 diabetes. Animal studies on metformin have suggested a possible link to the reduction of depression and anxiety, so this latest finding further suggests that further research into metformin and depression may be warranted.
Other genes identified in the study may have biologically plausible links to depression, such as a gene linked to a neurotransmitter involved in goal-directed behavior and genes that code for a type of protein previously linked to multiple neurological conditions.
Surprisingly, the researchers found less overlap than expected in genetic results for depressive disorder between ancestry groups, amounting to about 30% (based on a new method developed by the research team to assess the degree to which a genetic association found in an ancestry group). to another ancestry group), which has less overlap than previously found for other traits and diseases.
Therefore, it is even more important to study the disease in different samples because some of the findings may be specific to ancestry.
Lead author Professor Karoline Kuchenbaecker (UCL Psychiatry and UCL Genetics Institute) said: “Here we show beyond doubt that our understanding of complex diseases such as depression will remain incomplete until we overcome the Eurocentric bias in genetic research and look for the causes in different people around the world.”
“Many genes previously thought to be linked to depression risk may actually influence depression risk only in people of European descent, so for genetic research to contribute to new drugs that can help people of all backgrounds, it is vital that our heritage genetic data sets are appropriately diversified.”
Professor Kuchenbaecker added: “This is an early stage of discovery, so further work will be needed to confirm these new targets, but finding them in the first place was a huge and vital challenge, especially for a disorder where new drugs are so important.”
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