Researchers from the University of Colorado Boulder are calling for scientists to abandon candidate gene hypotheses for major depressive disorder after finding the 18 most studied candidate genes for depression are no more linked with the disorder than randomly chosen genes.
They published their findings online in The American Journal of Psychiatry.
“We are not saying that depression is not heritable at all. It is,” said associate professor Matthew Keller, PhD, senior author of the study. “What we are saying is that depression is influenced by many, many variants, and individually each of those has a miniscule effect.”
The study, which used genetic and survey data for 620,000 people, focused on 18 candidate genes mentioned in at least 10 previous studies. Researchers investigated whether any of the genes or gene variants were linked with depression either alone or combined with environmental factors such as 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,” Dr. Keller said. “The results, even to us, were a little bit stunning.”
Dr. Keller and colleagues are not advocating an end to research into the underpinnings of depression. Rather, they support a broader view that acknowledges the thousands of genes associated with the disease. With a more thorough understanding, they reasoned, more accurate polygenic scores could one day be used to predict depression risk and, perhaps, even guide drug development.
“This study confirms that efforts to find a single gene or handful of genes which determine depression are doomed to fail,” said lead author Richard Border, MA, a graduate student and researcher at the university’s Institute for Behavioral Genetics.
“It’s like in The Emperor Wears No Clothes,” Dr. Keller added. “There’s just nothing there.”
Border R, Johnson EC, Evans LM, et al. No support for historical candidate gene or candidate gene-by-interaction hypotheses for major depression across multiple large samples. The American Journal of Psychiatry. 2019 March 8;[Epub ahead of print].