It's estimated that 20 percent of Americans have experienced depression and that about four percent of the global population is depressed. Genetic factors are known to play some role. By analyzing genetic and health data from over a million people, researchers have now learned more about some of the genetic factors that raise the risk of depression. Depression is known to be difficult to treat, and that's partly because we don't know a lot about its biological basis This research, which relied on biobank data from the Veterans Affair's (VA) Million Veteran Program (MVP), 23andMe, and some others, may help change that. When scientists can study that much data, they can see trends that are far more difficult to discern from small groups. The findings have been reported in Nature Neuroscience.
"This study uncovered more of the genetic architecture of depression than was previously known," said co-primary investigator Dr. Joel Gelernter of the VA Connecticut Healthcare System and Yale University School of Medicine. "This implicates new regions of the genome for more targeted investigation and allows us to use this information to identify drugs that are currently approved for other indications and might be repurposed for treatment of depression."
This research was a genome-wide association study (GWAS), which assesses how much influence a small variation in the genetic sequence has on some trait. It's the first study to look at the impact of gene variations on depression in over one million people. The work revealed 178 genomic locations or loci that play a role in depression risk, 77 of which are newly identified. At those 178 loci, there were 223 changes in individual base pairs in the genome - single nucleotide polymorphisms or SNPs that raise a person's risk of getting depression.
The conclusions were more reliable because the findings from one database could be checked against another.
"One of the underappreciated elements of GWAS is how reproducible the findings are," explained co-lead study author Dr. Daniel Levey of the VA Connecticut Healthcare System and Yale University School of Medicine. "Now that we've achieved adequate power, we are finding great consistency in findings from different groups' study. We hope this consistency provides a stable foundation for new discoveries that can improve treatments."
Additional work confirmed previous findings that depression has some overlap with other mental disorders like anxiety, PTSD, engaging in risky behaviors, and cannabis use disorder.
"This study, like many before it, highlights the value of the MVP sample in identifying genes for common genetic traits, especially those that are important in the veteran population. Another unique value of the MVP is that it allows us to study populations other than Europeans. We didn't find nearly as much in African-ancestry subjects as in European-ancestry, but we made a good start, and our results will be of great value in future meta-analysis efforts," said Gelernter. "This is a critical advantage of the MVP."
Learn more about enrolling in the MVP here.
Hopefully, this work will be useful in the search for better treatments for depression. If we can learn more about how the genetic variations are impacting biology, we may know more about correcting the problem. There may also be existing drugs that work on these genes that could be repurposed for treating depression. A medication for amyotrophic lateral sclerosis (ALS) acts on one of the genes identified in this study, for example.