Several new gene variants have been identified as increasing the risk factor for depression, in the largest genetic analysis of the condition to date.
The study, carried out by Veterans Affairs (VA) researchers, provides a better understanding of the biological basis of depression, which could lead to better drug treatments. Involving genetic data on more than 300,000 participants of VA’s Million Veteran Program (MVP), as well as more than a million subjects from other biobanks, the researchers were able to spot trends in genetic risk of depression not previously known.
The findings have been published in the journal Nature Neuroscience.
Major depressive disorder
To date, research has demonstrated that genetics play a large role in depression risk. To understand exactly which genes are involved, the research team first analysed the genomes of over 250,000 MVP participants of European ancestry. They then combined the findings with previous analyses from several other genetic repositories including the UK Biobank, FinnGen, and 23andMe, with further subjects from other biobanks making for a total of more than 1.2 million participants.
The analysis revealed 178 loci – specific parts of the genome – that are involved in a person’s risk for depression, including 77 loci not previously detected in research. It also identified 223 single nucleotide polymorphisms (SNPs) – which is a specific variation of a single DNA building block – at these 178 locations that appear to affect a person’s depression risk.
Co-primary investigator Dr Joel Gelernter, a researcher with the VA Connecticut Healthcare System and Yale University School of Medicine, said: “This study uncovered more of the genetic architecture of depression than was previously known. 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.”
The researchers also examined the genomes of nearly 60,000 Veterans of African ancestry in the MVP database. They found that 125 of the SNPs identified in the European ancestry group (61%) directly affected the African ancestry participants’ risk for depression.
“One of the underappreciated elements of genome-wide association study (GWAS) is how reproducible the findings are,” added co-lead 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.”
Overlapping disorders
The analysis also revealed genetic overlap between depression and a number of other psychiatric conditions, including anxiety disorders and PTSD, as well as with risky behaviour and cannabis use disorder, the study found.
The team say that the findings could be used to identify new drug therapies for treating depression, as, by identifying what genes are involved in depression, existing drugs that are known to act on these genes could be repurposed.
“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,” Gelernter said. “This is a critical advantage of the MVP.”
