A team of US scientists claim that no specific set of genes can predict the risk of depression, and efforts to treat the mental disorder by targeting a few genetic culprits is bound to fail.
The researchers, who assessed genetic and survey data from 620,000 individuals, found that the 18 most highly-studied candidate genes for depression are actually no more associated with it than randomly chosen genes.
Over the past quarter-century, researchers have published hundreds of studies suggesting a small set of particular genes or gene-variants plays a substantial role in boosting susceptibility to depression. Such research fuelled hopes that clinicians could soon use genetic testing to simply identify those at risk, and drug companies could develop medications to counteract a few genetically-driven culprits, researchers said in a statement.
According to the team from the University of Colorado Boulder in the US, previous studies were incorrect or “false positives” and the scientific community should abandon what are known as “candidate gene hypotheses”.
“This study confirms that efforts to find a single gene or handful of genes which determine depression are doomed to fail,” said Richard Border, a graduate student at University of Colorado Boulder.
Depression is influenced by many variants
“We are not saying that depression is not heritable at all. It is. What we are saying is that depression is influenced by many many variants, and individually each of those has a miniscule effect,” said Matthew Keller, an associate professor at University of Colorado Boulder.
For the study, published in the American Journal of Psychiatry, researchers looked at 18 genes which have appeared at least 10 times in depression-focused studies.
Among them was a gene called SLC6A4, involved in the transport of the neurochemical serotonin. Research dating back 20 years suggests that people with a certain “short” version of the gene are at significantly greater risk of depression, particularly when exposed to early life trauma.
The researchers also looked at genes involved in the production of brain-derived neurotrophic factor (BDNF) a protein involved in nerve formation, and the neurotransmitter dopamine.
Childhood trauma?
Using genetic and survey data gathered from individuals via the UK Biobank, 23andMe, and the Psychiatric Genomics Consortium, they set out to see if any of the genes, or gene variants, were associated with depression either alone or when combined with an environmental factor like childhood trauma or socioeconomic diversity.
“We found that, as a set, these candidate genes are no more related to depression than any random gene out there,” said Keller. Keller said that in the field of genetics, scientists have known for years that candidate-gene hypotheses were flawed.
However, hopeful researchers in other fields, including psychology, have continued to publish studies — often based on smaller sample sizes — which have kept the idea of a small set of “depression genes” alive.
“Its like in The Emporer Wears No Clothes. Theres just nothing there. I hope this is the final nail in the coffin for those kind of studies,” said Keller.