New study identifies 44 genomic variants associated with depression

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This study is the largest genome-wide association study to date of genetic risk factors for major depression.

This “Manhattan plot” shows the locations of the 44 major depression loci on the human genome. The vertical axis shows statistical significance. The higher the more significant. Everything shown above the red horizontal line is statistically significant. Credit: UNC Healthcare
This “Manhattan plot” shows the locations of the 44 major depression loci on the human genome. The vertical axis shows statistical significance. The higher the more significant. Everything shown above the red horizontal line is statistically significant. Credit: UNC Healthcare

In a massive collaborative effort, scientists from 161 institutions across the world have identified 44 genomic risk variants associated with major depression. This is the largest genome-wide association study to date of genetic risk factors for major depression.

The research involved more than 200 researchers who work with the Psychiatric Genomics Consortium and was co-led by Patrick Sullivan of the University of North Carolina School of Medicine and Naomi Wray of the University of Queensland.

The new meta-analysis study was published on April 26th in Nature Genetics.

The publication maps genetic risk variants from more than 135,000 individuals who self-reported with major depressive disorder and includes more than 344,000 controls. Datasets from the US, UK, Iceland and Denmark were analyzed to underpin the major genetic variants, or gene loci, linked with depression.

Of the 44 loci, 30 were newly discovered in this study while 14 had been previously identified. In addition, the study identified 153 significant genes and found that major depression shared six loci that are also associated with schizophrenia.

“This study is a game-changer,” Sullivan said.

“Figuring out the genetic basis of major depression has been really hard. A huge number of researchers across the world collaborated to make this paper, and we now have a deeper look than ever before into the basis of this awful and impairing human malady. With more work, we should be able to develop tools important for treatment and even prevention of major depression.”

Importantly, the research confirms and highlights the genetic basis for depression, and also uncovers potential biological mechanisms that result in complex psychiatric illnesses. This could lead to better treatment approaches for those who are at increased risk of suffering depression.

“We show that we all carry genetic variants for depression, but those with a higher burden are more susceptible,” Wray said. “We know that many life experiences also contribute to the risk of depression, but identifying the genetic factors opens new doors for research into the biological drivers.”

In addition, the study found that the genetic basis for depression overlaps with other psychiatric disorders such as schizophrenia and bipolar disorder, and interestingly, with predisposing factors for obesity and impaired sleep quality.

Some of the gene variants identified could lead to a better understanding of the development of depression, paving the way to the next generation of drugs targets. However, further research will be required to confirm that the newly identified risk variants do indeed compound in depressive disorder.

“What we’ve had in recent decades is a shortage of new mechanisms that underlie depression and psychiatric disorders,” says Gerome Breen, a co-author on the paper.

“The hope is that in new data we identify new processes that can be targeted by newly developed types of drugs, which have different mechanisms of action to existing medications.”

Source: UNC Press Release