Genetic Risk Factors IDed for Depression Can Boost Drug Therapies

Using genomic data, researchers identified genetic risk factors for depression, according to a study published in Nature Neuroscience. The results show potential for identifying new drug therapies and utilizing existing drugs that target the same genes.

The study drew from patient data from over 300,000 Veterans in the Million Veteran Program, the US Department of Veterans Affairs’ research program that focuses on analyzing how military exposure, lifestyle, and genes can impact health, according to its website. They also analyzed genetic data from FinnGen, 23andMe, and the UK Biobank. There were more than 1.2 million participants in the primary study.

Researchers conducted a genome-wide association study (GWAS), which allowed them to analyze gene variants in the genomic codes of the study subjects with depression to see what they had in common. They started by analyzing 250,000 participants of European ancestry. The GWAS identified “178 genetic risk loci and 223 independently significant single-nucleotide polymorphisms (SNPs),” the study stated.

“We used genomic structural equation modeling (gSEM) to examine shared genetic architecture and pleiotropy among complex traits. We also investigated functional consequences through fine-mapping analysis, transcriptomic enrichment with respect to multiple brain tissues and functional annotation. The results provide a deep look into the genetic architecture of depression and its underlying complex biology.”

Next, researchers analyzed genomic data from 60,000 Veterans of African ancestry and found that 61 percent of the SNPs that affected depression in the European ancestry cohort also affected the African ancestry cohort. Researchers confirmed the results by cross-checking them with 1.3 million additional genome samples from 23andMe.

While genome research surrounding depression has been done in the past, this study’s vast sample size allowed researchers to find additional genetic risk factors than previously investigated. The results could be useful in repurposing existing drugs as treatment for depression.

One of the major takeaways is that the study “uncovered more of the genetic architecture of depression than was previously known," said study co-investigator Joel Gelernter, MD, of the VA Connecticut Healthcare System and Yale University School of Medicine, in a press release. "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."

Specifically, researchers “found overlapping biology with existing drugs—notably, those that affect glutamatergic function but also those that influence the actions of estrogen—that could offer repurposing opportunities,” the study stated. Results also revealed that depression had overlapping genetic risk factors with other psychiatric conditions, such as PTSD.

With millions of people worldwide experiencing depression, developing new treatments for mental health is a major industry focus. Another recent study also conducted a GWAS and identified 25 brain proteins that show promise as targets for treatment. Additionally, recent research looked at using precision medicine for mood disorders. The researchers developed a blood test consisting of RNA biomarkers and were able to predict and treat mood disorders.

Precision medicine, artificial intelligence, and the identification of genetic risk factors have the potential to provide concrete data that would otherwise be difficult to pinpoint. These developments could have a significant impact on mental healthcare, improving treatment and quality of care for millions.