Origins of depression highlighted in large-scale genetic study

Hundreds of genes have recently been linked to depression, shedding light on the origins of the condition and highlighting the personality types that may be at risk.

The international study, involving more than two million people, is the largest of its kind. It could shed light on treatments for the condition, which affects one in five people in the UK and is the leading cause of disability worldwide.

Scientists led by the University of Edinburgh studied information pooled from three large datasets of anonymized health records and DNA and identified 269 genes linked to depression.

They also used an innovative statistical method to identify sections of DNA that were common in people with depression and in those who engaged in lifestyle behaviors such as smoking.

The results suggest depression could be a factor leading some people to smoke, but more research is needed to explain why, the team say.

The results also show that neuroticism – a tendency to worry or be afraid – could lead people to become depressed, which could shed light on the personality factors that put people at risk.

The statistical approach – known as Mendelian randomization – allows scientists to examine the impact of a condition on behavior, while ruling out other influences such as age or income.

Anonymised data, used with donor consent, is held by UK Biobank, personal genetics and research company 23andMe and the Psychiatry Genomics Consortium.

Experts say the study reflects the importance of data science in understanding mental health and the leading role Scotland plays in it.

The team is inviting people with depression or anxiety in Scotland to take part in further study, to better understand the role of DNA in common mental health conditions.

The research – known as the GLAD (The Genetic Links to Anxiety and Depression) study – aims to better understand depression and anxiety in order to improve the lives of people with mental health conditions.

The team, together with colleagues from the National Institute of Health Research Mental Health BioResource and King’s College London, hope to collect saliva samples and questionnaires from 40,000 people across the UK.

Study participants will be offered the opportunity to participate in further mental health research.

The study, published in Natural neuroscience, was funded by Wellcome and the Medical Research Council.

Professor Andrew McIntosh, from the University of Edinburgh’s Center for Clinical Brain Sciences, who led the research, said: “These findings are further evidence that depression is partly down to our genetics.

“We hope that by launching the GLAD study, we can learn more about why some people are at higher risk than others for mental health problems, and how we could more effectively help people with depression. and anxiety in the future.”

Raliza Stoyanova, Lead Developer of Wellcome’s Neuroscience and Mental Health Portfolio, said: “This large study is an important step forward in understanding how genetic variability may contribute to the risk of depression. Given that current treatments only work for half of those who need them, the study provides intriguing clues for future research to follow – for example that the biological pathways involved in disease development may not be the same as those involved in response to treatment.”

Sophie Dix, director of research at mental health charity MQ, who was not involved in the research, said: “This study adds to the weight of evidence that genes are one of the main factors risk of depression, which is also affected by life events such as social environment and trauma.The value of this could really be seen by looking at the development of personalized treatments – a welcome step given the lack innovation in identifying new approaches.We have seen very little progress in nearly 50 years for people living with depression and currently the avenues available do not work for everyone.

“The power of this large genetic study is that it may point to systems in the brain that add to our currently limited understanding in this area. By increasing our understanding of these systems and how the social environment affects biological risk factors, we can begin to identify new targets for treatments that could help the millions of people around the world affected by depression.”

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