Treasure trove of 269 genes associated with depression identified

Written by Sharon Salt (Editor)

In the largest study of its kind, a team of international collaborators led by the University of Edinburgh (UK) have discovered hundreds of genes that have been newly linked to depression.
Within the study, which has been published in Nature Neuroscience, researchers meta-analyzed data on 807,553 individuals from the three largest genome-wide association studies of depression. They identified 102 independent variables, 269 genes and 15 genesets associated with depression, including both genes and gene pathways association with synaptic structure and neurotransmission.

Additionally, the team used an innovative statistical method – known as Mendelian randomization – to identify sections of DNA that were common in people with depression and in those who adopted lifestyle behaviors such as smoking.

The findings of the study suggest that depression could be a driving factor leading some individuals to take up smoking, however, the team caution that more research is needed to explain why.

Results also show that neuroticism – a tendency to be worried or fearful – could lead people to become depressed, which could shed light on personality factors that put people at risk.

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“This large study is an importance advance in understanding how genetic variability might contribute to risk for depression. Given that current treatments work for only half of those who need them, the study provides some intriguing clues for future research to follow up – for example that biological pathways involved in developing the condition may not be the same as those involved in responding to treatment,” explained Raliza Stoyanova (Wellcome).

To understand more about the role of DNA in common mental health conditions, the team are currently inviting people with depression or anxiety in Scotland to take part in a further study. The research – known as the Genetic Links to Anxiety and Depression (GLAD) study – aims to better understand depression and anxiety in order to improve the lives of people with mental health issues.

Investigators are hoping to collect saliva samples and questionnaires from 40,000 people across the UK and study participants will be offered the chance to take part in further mental health research.

Lead author of the study, Andrew McIntosh (University of Edinburgh), concluded: “These findings are further evidence that depression is partly down to our genetics. We hope that by launching the GLAD study, we will be able to find out more about why some people are more at risk than others of mental health conditions, and how we might help people living with depression and anxiety more effectively in future.”

Sources: Howard DM, Adams MJ, Clarke T-K et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat. Neurosci. doi:10.1038/s41593-018-0326-7 (2019) (Epub ahead of print); www.ed.ac.uk/news/2019/depression-s-origins-focus-of-huge-gene-study