Scientists discover 17 genetic variations that raise risk of depression

Scientists have discovered 17 separate genetic variations that increase the risk of a person developing depression.

The findings, which came from analysing DNA data collected from more than 300,000 people, are the first genetics links to the disease found in people of European ancestry.

The scientists say the research will contribute to a better understanding of the disease and could eventually lead to new treatments. They also hope it will reduce the stigma that can accompany depression.

According to Nice, up to 10% of people seen by practitioners in primary care have clinical depression, with symptoms including a continuously low mood, low self-esteem, difficulties making decisions and lack of energy.

Both environmental and genetic factors are thought to be behind depression, with the interaction between the two also thought to be important. But with a large number of genetic variants each thought to make a tiny contribution to the risk of developing the condition, unravelling their identity has proved challenging.

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While previous studies have turned up a couple of regions in the genome of Chinese women that might increase the risk of depression, the variants didn’t appear to play a role in depression for people of European ancestry.

But now researchers in the US say they have identified 17 genetic variations associated with the condition in Europeans, spread across 15 regions of the genome.

“It just underscores that depression really is a brain disease,” said Roy Perlis, the co-author of the research from Massachusetts general hospital. “Depression is about biology and I think that will be helpful for some people in reducing stigma and changing how we think about depression.”

To unpick possible genetic associations, the researchers examined data collected by the consumer genetic testing company 23andme. Of the 300,000 people studied, 75,607 self-reported a clinical diagnosis of depression or were receiving treatment for the condition.

By comparing the frequency of common genetic variations in the people with depression compared to those without, the scientists discovered two genomic regions associated with the condition, one of which has previously been linked to epilepsy and intellectual disability.

Further analysis, including 23andme data from another 150,000 individuals, as well as clinical data from a worldwide multi-institutional collaboration involving nearly 19,000 individuals, threw up more results, with scientists identifying 17 genetic variants in 15 genome regions associated with depression. The findings are published in the journal Nature Genetics.

While the genetic variants found are thought to contribute, at most, a few percent to the overall risk for depression, the results are valuable, said Perlis. “It is a very small proportion of risk, this is not the sort of finding that can be used to make a diagnostic test or predict depression. The reason this kind of genetics is important is it points us towards a biology of disease,” he said.

Understanding what the genes do and how they interact could lead to better treatments for depression, Perlis continued. “In general that would tend to make it less likely rather than more likely that we would find [genetic] associations,” he said, adding that the researchers found a strong link in the cohort between depression and other related conditions such as anxiety, obesity and sleeplessness. “These are the people who ultimately we would like to be able to develop other treatments for – not research participants, but people who get diagnosed with depression and treated for depression.”

Elisabeth Binder from the Max Planck Institute of Psychiatry in Germany, and who was not involved in the study, agrees. “With this paper alone we cannot explain very much about depression but it is the first really substantial and valid genetic hits and now we can go in and look at these hits, look at connected hits and really start to understand the disease,” she said.

But, says Binder, the new research doesn’t shed light on sub-groups of depression, while it is likely that there are many genetic variants associated with depression that have not yet been found. However, she believes the new results could help researchers probe how genetic and environmental risk factors are connected.

What’s more, she says, with each genetic variant thought to contribute only a minuscule increase in risk for the disorder, and huge sample sizes needed to spot them, the research highlights the value of data from genetics companies. “I think the beauty of this study is that they were using data from the company 23andme and thereby really boosted the sample sizes in numbers that were unachievable using other types of studies that were ongoing in the regular research community,” she said.

But Jonathan Flint, from the University of California in Los Angeles, warns that the use of data based on self-reports of diagnosis is problematic. Not only are many individuals with major depressive disorders likely to never have received a diagnosis, others might have been diagnosed who do not meet the criteria for the condition.

“What we might be identifying here is something much more to do with help-seeking behaviour than anything to do with a psychiatric illness,” he said.

Scientists discover 17 genetic variations that raise risk of depression