New clues to genetics of depression are ‘game-changing’

New research shows "that we all carry genetic variants for depression, but those with a higher burden are more susceptible."

Researchers have identified 44 genomic variants, or loci, with a statistically significant association with depression. The meta-analysis involves research with more than 135,000 people with major depression and more than 344,000 controls.

Of these 44 loci, 30 are new discoveries while previous studies had identified 14 of them. In addition, the new study in Nature Genetics identifies 153 significant genes, and found that major depression shared six loci that are also associated with schizophrenia.

“Major depression represents one of the world’s most serious public health problems.”

“This study is a game-changer,” says study co-leader Patrick F. Sullivan, professor of psychiatry and genetics and director of the Center for Psychiatric Genomics at the University of North Carolina School of Medicine.

“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.”

“We show that we all carry genetic variants for depression, but those with a higher burden are more susceptible,” says study co-leader Naomi Wray, professorial research fellow at the University of Queensland.

“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.”

Other findings of the study include:

  • The results can be useful for improved therapies, as targets of known antidepressant medications were enriched in the genetic findings
  • The genetic basis of depression overlaps importantly with other psychiatric disorders like bipolar disorder and schizophrenia
  • 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.

“Major depression represents one of the world’s most serious public health problems,” says Steven E. Hyman, former director of the US National Institute of Mental Health who is now director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard. He is not an author of the paper.

“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,” Hyman says.

The work involved over 200 scientists who work with the Psychiatric Genomics Consortium.

Funding for the primary studies included in the meta-analysis came from the US National Institute of Mental Health and National Institute on Drug Abuse; Netherlands Scientific Organization, Dutch Brain Foundation, and the VU University Amsterdam; Federal Ministry of Education and Research (Germany), Deutsche Forschungsgemeinschaft (DFG, German Research Foundation); the Swedish Research Council; and National Health and Medical Research Council (Australia).

Source: UNC-Chapel Hill

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