Although depression is a common disorder that affects 280 million people worldwide, according to the World Health Organization (WHO), and can have consequences as serious as suicide, its effects are still not well understood. Causes. Now, the first large-scale global study on the genetics of major depression in participants of different ancestry has identified 205 new genes associated with this mental health problem, which represents an important advance in finding new treatments.
The research has been carried out by an international team led by scientists from University College London (UCL) and has shown the potential of reusing drugs that are already used to treat other diseases, since one of the identified genes encodes a protein that is directs a common drug for diabetes, in addition to targeting new therapeutic targets to develop drugs to treat depression. The results have been published in Nature Genetics.
Genetic research using big data provides new avenues for understanding this pathology and has discovered dozens of genes associated with depression, each of which individually confers only a small increase in risk. It may also help find new drug targets, but so far research has focused primarily on people of European descent, something researchers say is a major shortcoming, especially for a condition as complex as depression.
Therefore, the new work included multiple methods of genetic research, and the researchers reviewed genetic data from 21 study cohorts from several countries, and almost one million study participants were of African, East Asian, South African and African descent. Asian and Hispanic/Latin American, including 88,316 people with major depression.
A diabetes drug that could combat depression
The study has made important progress in identifying genes related to the risk of depression, both through newly identified links and by strengthening previous evidence, and shows some genes with possible implications for drug development, such as NDUFAF3. The protein encoding NDUFAF3 has previously been implicated in mood instability and is the target of metformin, the first-line drug for the treatment of type 2 diabetes. Animal studies on metformin have suggested a possible link with a reduction in depression and anxiety, so this latest finding further suggests that additional research into metformin and depression may be warranted.
Surprisingly, the researchers found less overlap than expected in the genetic matches for depression between ancestry groups, about 30% (according to a new method developed by the research team, to measure the degree to which a genetic association found in a ancestry group is applicable to another ancestry group), which has less overlap than previously found for other traits and diseases. Therefore, it is even more important to study depression in diverse samples because some of the findings could be ancestry-specific.
“Many genes that have previously been linked to depression risk may actually only affect depression risk in people of European origin.”
Lead author Professor Karoline Kuchenbaecker (UCL Psychiatry and UCL Institute of Genetics) said: “Here we show, without a doubt, that our understanding of diseases as complex as depression will remain incomplete until we overcome bias.” “Eurocentric in genetic research and look for causes in diverse people around the world.”
“Many genes that have previously been linked to depression risk might actually only affect depression risk in people of European origin, so for genetic research to contribute to the development of new drugs that can help people of different ancestry , it is essential to analyze diverse genetic data sets”
“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 has been a huge and vital challenge, especially for a disorder where new drugs are so desperately needed.” urgency,” concludes Kuchenbaecker.
