Study Identifies the Genes That Increase Your Risk of Depression

Even though over 200 million people worldwide are estimated to have depressive disorders, the biology behind what causes these conditions is still not fully understood. Scientists are increasingly looking toward genetics.

A new study identified 178 gene locations linked to major depression—77 more than scientists had previously discovered. This is the largest genome-wide association study on depression to date.

Identifying this chunk of genes can help assess a person’s risk of becoming depressed. And researchers suspect that there could be more genes to add to this pool too.

For the study, scientists analyzed the health records of over 1.2 million people from four different data banks to look for genetic similarities and patterns among people affected by depression.

“We've known for many years that risk for depression is genetically influenced," study co-author Joel Gelernter, MD, the Foundations Fund Professor of Psychiatry at Yale University, tells Verywell. "There's an environmental component to risk, which includes things like adverse life events, and there's a genetic component to the risk. It's only relatively recently that we, in the field, have started to identify what some of the specific risk genes and risk variants are.”

Findings like these can help scientists better pinpoint the biological roots of depression. They're hopeful these findings could one day assist in:

• Identifying which parts of the population that are more at risk of depression
• Determining who could benefit from early intervention
• Helping develop and carry out better drug treatments

The research appeared in the journal Nature Neuroscience in May.

Why Examine Genes Linked to Depression?

Depression is a clinical condition that causes people to feel upset, hopeless, and sad—sometimes for no apparent reason. Almost 10% of Americans will be affected by depression each year.

Although research in the field is constantly advancing, scientists still don’t know what the exact biological, genetic, psychological, and environmental conditions contributing to the disorder are. There isn’t a one-size-fits-all recipe for preventing or treating depression. 

Scientists have looked into the “depression gene” for about 50 years now, and several studies on the hereditary patterns of depression have been conducted throughout this period of time.

“For instance, twin studies suggest a heritability of up to 50%, and family studies up to a three-fold increase in lifetime risk of developing major depression in first degree relatives,” Caroline Carney, MD, MSc, FAMP, chief medical officer at Magellan Health, who was not involved in the study, tells Verywell.

An understanding of the genetic underpinnings of depression will help us better understand, for instance, why some persons can weather stressors better than others, or why some persons become depressed for no apparent reason, Carney says.

However, like several other mental health disorders, depression is characterized by a complex genetic combination of variants that still needs to be fully understood.

“It's taken a long time to get to this point because depression is very complex genetically,” Gelernter says. “Unlike traits that are controlled by single dominant or recessive genes—which to a first approximation might include something like eye color—depression is genetically complex. Meaning that there are many, many risk genes, none of which comes at all close to determining if a person is going to become depressed or not.”

Certain Genes Can Increase Risk

To dig deeper into the genetics of depression, researchers from the U.S. Department of Veterans Affairs at Yale University School of Medicine and the University of California-San Diego analyzed genomic records and medical records from four different databases.

They conducted a meta-analysis of the records from more than 300,000 participants.

Their in-depth analysis revealed 178 specific parts of the genome, known as “loci”, are somehow linked to a person's risk for depression. Seventy-seven of these were brand new loci that had not previously been identified.

The analysis also identified 223 specific variations of DNA blocks—called single-nucleotide polymorphisms or SNPs (pronounced “snips”)—at these 178 locations that also appear to affect a person's depression risk. 

Each gene individually only slightly increases or decreases risk, Gelernter explains. “So…you have many risk variants, each of which predisposes you a little bit,” Gelernter says. “Simply put, the effects of these different risk variants can come together and place you at higher risk for depression, still most likely in the context of environmental stressors.”

What Does This Mean for Future Depression Treatment?

“As we identify more and more genetic variants and genes that influence risk, we get a fuller and fuller picture of the underlying biology," Gelernter says. "And with a better understanding of biology, the goal is that eventually, we can develop better treatments."

He says that understanding the genetics of depression can be helpful for treatment on two main fronts:

• Developing new treatments. Pharmaceutical companies could look at the biology revealed in the study and target some of the specific molecules that were identified.
• Drug repurposing. There are drugs that are already approved for various uses and, through research like this, scientists can identify if any might be good matches for treating depression.

“This type of information provides yet another piece of the puzzle in our understanding of depression and the role of genetics and the brain by confirming previous findings, and adding new information,” Carney says.

According to her, this research should also further help combat the stigma associated with behavioral health disorders such as depression.

Both Carney and Gelernter explain that, while the science is still evolving and more research in the field is needed, the potential to design therapies specifically targeted to the biology of depression is in the near future. When asked if we're talking about years or decades, according to Gelernter, it could be as close as in the next ten years.