Diverse genomes cast light on depression identified

More than 200 new genes associated with depression have been identified in the first large-scale genome-wide association study to include participants from diverse ancestry groups.

Major depression, also known as clinical depression, is a complex disease with large clinical demand but limited understanding of its root causes. Led by researchers at University College London (UCL), a study that examined the genomes of one million participants has identified 53 new gene loci and functionally mapped 205 new genes significantly associated with major depression. It marks the first study on this scale to include participants beyond European ancestry.

'Many genes previously found to be linked to the risk of depression might only actually affect depression risk in people of European origin, so in order for genetic research to contribute to new drugs that can help people of all ancestries, it is vital that our genetic datasets are suitably diverse' said Karoline Kuchenbaecker, professor of genetic epidemiology at UCL and lead author of the paper published in Nature Genetics.

The UCL team collaborated with researchers worldwide to gather data from 21 cohorts spanning African, East Asian, South Asian, and Hispanic/Latin American groups. Among the participants, 88,316 had major depression, while 902,757 served as controls.

Major depression was defined using medical care records, symptom questionnaires, self-reported surveys and clinical interviews. The data collected from all participants was then gathered with data from previous studies.

The findings revealed that only 30 percent of genetic associations observed in European ancestry groups could be extrapolated to these wider populations, a lower proportion than anticipated. This underscores the importance for inclusive, multi-ancestry research approaches to better understand genetic factors contributing to the disorder.

A key discovery from the study is the association between a gene called NDUFAF3 and depression. This gene serves as the primary target of metformin, a first-line drug used to treat type 2 diabetes. The finding aligns with prior research in animal models which indicated a connection between administration of metformin and a reduction in depression and anxiety.

Furthermore, work carried out by scientists at the University of Surrey, identified seven genetic variants that are linked to both depression and diabetes (see BioNews 1206). These genetic associations could potentially pave the way for novel drug targets, or re-purposing of existing drugs, to improve clinical care of major depression.

'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 medications are so urgently needed,' said Professor Kuchenbaecker.