The "genes of depression" turned out to be empty
The hypothesis about the "gene of depression" has been refuted
Lina Medvedeva, XX2 century
Over the past 25 years, hundreds of studies have been published claiming that a small set of specific genes or their variations play a significant role in increasing susceptibility to depression. Such studies have raised hopes that doctors can use genetic testing to identify those at risk, and pharmaceutical companies will develop drugs to combat the culprit genes.
However, a new study of genetic data and survey data of 620000 people conducted at the University of Colorado at Boulder (Study debunks 'depression genes' hypotheses) showed that the 18 most studied candidate genes are associated with depression no more than randomly selected genes.
The results of the work do not confirm earlier studies, during which "depression genes" were allegedly discovered, in addition, it is noted that these "discoveries" were made when studying orders of magnitude smaller samples. The size of the current study makes the probability of a phenotypic error, that is, the influence of individual, not directly caused by the genome, characteristics of the subjects on an almost zero result, very unlikely.
"This study confirms that attempts to find a single gene or several genes that determine depression are doomed to failure," says the study's lead author, Richard Border, a graduate student at the Institute of Behavioral Genetics.
Matthew Keller, Associate Professor of Psychology and Neurology adds: "We are not saying that depression is not inherited, it is inherited. We argue that the occurrence of depression is influenced by many variations of genes, each of which brings a small effect."
For the study published in the American Journal of Psychiatry (No Support for Historical Candidate Gene or Candidate Gene-by-Interaction Hypotheses for Major Depression Across Multiple Large Samples), the authors examined 18 genes mentioned at least 10 times in depression studies. Among them was the SLC6A4 gene involved in serotonin transport. Studies conducted 20 years ago suggested that people with a "short" version of the gene are at significantly greater risk of depression, especially those who experienced trauma in childhood.
The researchers also looked at genes involved in the brain's production of neurotrophic factor, a protein involved in nerve formation and the neurotransmitter dopamine.
Using genetic and survey data obtained from the UK Biobank, a company engaged in genetic testing and analysis, 23andMe and Psychiatric Genetic Consortium (Psychiatric Genomics Consortium), scientists have tested whether any individual genes or gene variations are associated with depression or in combination with environmental factors, such as childhood trauma or socio-economic status.
The study is the largest and most comprehensive to date, which examines the effect of certain genes on depression.
"We found that these genes are no more associated with depression than any other randomly selected gene," says Keller. "The results were a little surprising for us."
Keller notes that experts in the field of genetics have long known that hypotheses about the influence of a certain gene on depression are erroneous. But researchers from other fields, including psychology, will continue to publish studies based on a small sample, preserving the idea that there are a certain number of "depression genes."
"It's like a case of 'and the king is naked...'" says Keller. "I hope this is the last nail in the coffin of such research."
Border also emphasizes that such results do not mean that research on the genetic basis of depression should be discontinued. But, it should be recognized that the genetic architecture of depression is more complex than previously assumed. If we understand the thousands of genes associated with this disease, which scientists are doing, then eventually we can come to more accurate "polygenic estimates" for predicting risk and developing drugs designed to counteract this risk.
At the same time, according to Border, people should be wary of claims that individual genes have a strong influence on complex behavior. Although the risk of certain diseases, such as breast cancer and Alzheimer's disease, is clearly associated with individual genes, depression is not so simple.
"Every time someone claims to have identified a gene that causes a complex trait, you have to be skeptical about it," Border says.
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