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Are there "depression genes"? It's not that simple, concludes new study CU Boulder today



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Over the last quarter of a century, scientists have released hundreds of studies suggesting a small set of particular genes or gene variants, playing a major role in increasing sensitivity to depression. Such papers were hoping that clinicians could quickly use genetic testing to merely identify the risks and drug companies could develop medications to counteract some genetically engineered sinners.

However, a new CU Boulder study, which evaluated genetic and study data from 620,000 individuals, found that the 1

8 most studied candidate genes for depression are in fact no longer associated with it than randomly selected genes.

The previous studies were wrong or "false positives" – and the scientific community should abandon what is known as "candidate hypotheses", the authors conclude.

"This study confirms that efforts to find a single gene or a handful of genes that determine depression are doomed to failure, says lead author Richard Border, a graduate student and researcher at the Department of Behavioral Genetics.

Matthew Keller, Associate Professor of Psychology and Neuroscience: "We do not say that depression is not hereditary at all. It is. What we say is that depression is influenced by many variants, and each one has a minor effect. "

For the study, published in American Journal of Psychiatry (PDF) The authors looked at 18 genes that 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 The research goes back 20 years suggesting that people with a particular "short" version of the gene have a significantly greater risk of depression, especially when exposed to trauma in early life.

Every time someone claims having identified the gene that causes "a complex trait is a time to be skeptical." -Richard Border

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

Using genetic and study data collected from individuals via UK Biobank, 23andMe and Psychiatric Genomics Consortium, they set out to see if any of the genes or gene variants were associated with depression either alone or in combination with an environmental factor such as childhood trauma or socioeconomic diversity.

The study is the largest and most comprehensive study to date for historical depression candidate genes. [19659003] "We found that these candidate genes as a set are no more related to depression than any random gene out there," Keller said. "The results, even for us, were a bit amazing."

Keller notes that in genetics, researchers have known for years that candidate genes hypothesized was flawed. But hopeful scientists in other fields, including psychology, have continued to publish studies – often based on smaller sizes – that have kept the idea of ​​a small set of "depression genes" alive.

"It's like in The Emperor wears no clothes . There's just nothing there," said Keller. "I hope this is the last stitch in the coffin for those kinds of studies."

He and Border emphasize that their results do not mean that research into the genetic support of depression should cease. Instead, they say it should recognize that the genetic architecture of depression is more complicated than once believed. By understanding the thousands of genes associated with the disease and what they do, scientists can ultimately provide more precise "polygenic scores" to anticipate risk and potentially develop drugs designed to counteract this risk. they said.

In the meantime, Border says that consumers should be cautious about claiming that individual genes have great effects on complex behavior. While the risk of some medical conditions, such as breast cancer and Alzheimer's disease, has been clearly associated with individual genes, features such as depression are not so simple.

"Every time someone claims to have identified the gene that & # 39; causes a complex trait is a time to be skeptical," Border said.


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