Over the past 25 years, researchers have published hundreds of studies suggesting that a small set of particular genes or gene variants play an important role in increasing susceptibility to depression . These documents fueled the hope that clinicians could soon use genetic testing to simply identify people at risk, and that drug companies could develop drugs to counter a few culprits of genetic origin.
But a new study by CU Boulder evaluating genetic and survey data from 620,000 people revealed that the 18 most-studied depression-prone genes are actually no more associated than randomly selected genes.
Previous studies were incorrect – or "false positives" – and the scientific community should abandon what are called "hypotheses of candidate genes," the authors conclude.
"This study confirms that efforts to find a single gene or a handful of genes that determine depression fail," said lead author Richard Border, a graduate student and researcher at the Institute for Behavioral Genetics.
Matthew Keller, associate author in psychology and neuroscience, added, "We are not saying that depression is not hereditary at all. It is. What we are saying is that depression is influenced by many variations and that each of them has a minimal effect. "
For the study published in the American Journal of Psychiatry (PDF), the authors examined 18 genes that appeared at least 10 times in studies focused on depression. Among them was a gene called SLC6A4, involved in the transport of neurochemical serotonin. Research dating back 20 years suggests that people with some "short" version of the gene run a significantly higher risk of depression, especially when they are exposed to early trauma.
Whenever someone claims to have identified the gene that "causes" a complex trait, it becomes a skeptical moment. " -Richard Border
The researchers also examined the genes involved in the production of brain-derived neurotrophic factor (BDNF), a protein involved in the formation of nerves, and the neurotransmitter dopamine.
Using genetic data and surveys collected from individuals via the British Biobank 23andMe and the Consortium of Psychiatric Genomics, they sought to determine if any of these genes, or gene variants, was associated with depression alone or associated with an environmental factor such as childhood trauma or socio-economic diversity.
The study is the largest and most comprehensive study to date on historical candidate depression genes.
"We found that, overall, these candidate genes are no more related to depression than any random gene," said Keller. "The results, even for us, were a little surprising."
Keller notes that in the field of genetics, scientists have known for years that assumptions about candidate genes were skewed. But hopeful researchers in other areas, including psychology, have continued to publish studies – often based on smaller samples – that have maintained the idea of a small set of "genes of depression".
"It's like in The emperor does not wear clothes. There is nothing there, "said Keller. "I hope it's the last nail in the coffin for this kind of studies."
Border and he point out that their discoveries do not mean that research on the genetic underpinnings of depression must stop. Instead, they should recognize that the genetic architecture of depression is more complicated than previously thought. By understanding the thousands of genes associated with the disease and what they do, researchers can ultimately offer more accurate "polygenic scores" to predict risk and potentially develop drugs designed to counteract this risk, they said. .
In the meantime, he says, consumers should be wary of claims that certain genes have significant effects on complex behaviors. Although the risk of certain diseases, such as breast cancer and Alzheimer's disease, is clearly linked to individual genes, it is not so simple to present characteristics such as depression.
"Whenever someone claims to have identified the gene that" causes "a complex trait, it's a moment of skepticism," Border said.