Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

Of these 44 loci, 30 are newly discovered while 14 have been identified in previous studies. In addition, the study identified 153 significant genes, and found that major depression share six loci that are also associated with schizophrenia.

Other findings of the study include:

• The results can be used for improved therapies – targets of known antidepressant medications were enriched in the genetic findings
• The genetic basis of depression overlaps importantly with other mental disorders like bipolar disorder, schizophrenia, ADHD, and autism spectrum disorder
• Intriguingly, the genetic basis of depressive disorder also overlaps with that for obesity and multiple measures of sleep quality, including daytime sleepiness, insomnia and tiredness

The study was an unprecedented global effort by over 200 scientists from 161 institutions worldwide who work with the Psychiatric Genomics Consortium. The study, co-led by six principal investigators, including Patrick Sullivan of UNC, Naomi Wray of the Queensland Brain Institute and Anders Børglum of iPSYCH, is one of the largest genome-wide association studies to date of genetic risk factors for major depressive disorder. Several iPSYCH researches participated and are among the co-first and co-last authors of the paper. The iPSYCH contribution of cases with major depressive disorders was the largest single study of all.

BØRGLUM QUOTE: "The genomic variants and risk genes that have been identified open completely new windows into studying and understanding the underlying biology."

SULLIVAN QUOTE: “This study is a game-changer. 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.”

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

NIMH DIRECTOR JOSH GORDON QUOTE: “This pioneering study is incredibly important, for two reasons. First, it reaffirms the value of large-scale collaborations, particularly in identifying the complex genetics underlying psychiatric illness. Second, it confirms the genetic roots for depression, offering important biological clues that we hope will lead to new and better treatments.”

Steven E. Hyman, MD, former director of the U.S. National Institute of Mental Health, now Director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard: “Major depression represents one of the world's most serious public health problems and despite decades of effort there have been, until now, only scant insights into its biological mechanisms. This unfortunate state of affairs has severely impeded treatment development, leaving the many people who suffer from depression with limited options. This landmark study represents a major step toward elucidating the biological underpinnings of depression.”

The paper was published in Nature Genetics: ”Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression”.

More information in a press release from May 2018, click here