Good news! Will we finally defeat the demons of depression!
"... with 293 newly identified gene variants found to play a role in ramping up the risk factor. That's 42% more than was previously known.
A massive trans-ancestry genome-wide association study (GWAS) looked at the genetic makeup of 688,808 individuals with depression and 4,364,225 people in the control group and identified, in total, 697 variants across 635 gene loci linked to the disorder. 293 of those were new findings. ...
if a person is living with a full genetic bingo card of these identified variants, there's a much higher risk of them developing the disorder. ..."
"... Australia’s contribution to the international study was vital.
More than 50 of the newly identified gene variants came via results from the Australian Genetics of Depression Study (AGDS) which provided a database of 16,000 participants with depression and 18,000 without depression providing saliva samples for analysis. ...
The research team from the Psychiatric Genomics Consortium involved scientists from continents including the UK, South Africa, Brazil, Mexico, the USA, Australia, Taiwan and China. ..."
From the highlights and abstract:
"Highlights
• Trans-ancestry GWAS identified 697 variants and 308 genes associated with depression
• Implicates postsynaptic density, neuronal dysregulation, and amygdala involvement
• Findings enriched for antidepressant targets and highlight drug repurposing options
• Polygenic scores predicted depression case-control status across all ancestries
Summary
In a genome-wide association study (GWAS) meta-analysis of 688,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries across diverse and admixed ancestries, we identify 697 associations at 635 loci, 293 of which are novel.
Using fine-mapping and functional tools, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. A neural cell-type enrichment analysis utilizing single-cell data implicates excitatory, inhibitory, and medium spiny neurons and the involvement of amygdala neurons in both mouse and human single-cell analyses.
The associations are enriched for antidepressant targets and provide potential repurposing opportunities. Polygenic scores trained using European or multi-ancestry data predicted MD status across all ancestries, explaining up to 5.8% of MD liability variance in Europeans. These findings advance our global understanding of MD and reveal biological targets that may be used to target and develop pharmacotherapies addressing the unmet need for effective treatment."
Hundreds of new genes linked to depression in unprecedented global study (original news release)
Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies (open access)
Graphical abstract
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