Study Offers More Insights into the Genetics of Depression

A massive new genome-wide association study led by the U.S. Department of Veteran Affairs is shedding new light on the genetic underpinnings of major depression.

More than 16 million Americans are affected by depression each year, and nearly 6 million Americans suffer from bipolar, according to the National Institutes of Health. However, current treatment options do not always work for people living with these conditions, and researchers hope that new insights into the genetics of the condition could help in both diagnosing and treating it. 

Million Veterans

For this study scientists at Yale and the University of California, San Diego used data from 1.2 million people to identify 178 genetic variants linked to depression.  

The study, published in the journal Nature Neuroscience, included data from the Million Veteran’s Project, the UK Biobank, FinnGen, and from customers at 23andMe who consented to participate in research. After the initial study, the researchers cross-checked their findings using an entirely separate cohort from 23andMe that included data from 1.3 million customers who consented to participate in research.

“What is most heartening is that we could replicate our findings in independent data sets,” said Daniel Levey, an associate research scientist in the Yale Department of Psychiatry and co-lead author. “Replication is a hallmark of good science, and this paper points to just how reliable and stable results from GWAS studies are becoming.” 

Brain Development

A number of the genetic variants identified are giving researchers deeper insight into the underlying biology of depression. Researchers point to variants in or near the gene NEGR1, which is a neural growth regulator active in the hypothalamus, an area of the brain previously linked to depression. 

That confirms research done by the late Yale neuroscientist Ronald Duman on the role of neurotrophic factors in depression, Levey said.

“It’s really striking when completely different kinds of research converge on similar biology, and that’s what’s happening here,” he said.

The size and breadth of the study will also help scientists create models to calculate risk — known as polygenic risk scores — to better estimate the risk for developing major depression or other related psychiatric disorders such as post-traumatic stress disorder and anxiety. Beyond estimating the risk, the hope is that new genetic insights will help in identifying better ways for treating depression and related conditions.

“One of the real goals of the research is bringing forward new ways to treat people suffering from depression,” said co-senior author Dr. Murray Stein, staff psychiatrist at the V.A. San Diego Healthcare System and Distinguished Professor of Psychiatry and Public Health at UCSD.