International scientists have identified 44 genetic variants that can increase the risk of developing major depression - and found that all humans carry at least some of them.
The new findings could help explain why not everyone treated with antidepressants sees their condition improve, the scientists said, and could also point the way towards new medicines.
In the largest study of its kind, scientists also found that the genetic basis for depression is shared with other psychiatric disorders such as schizophrenia - and that a number of the variants are linked to the targets of antidepressant drugs.
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Major depression affects around 14 percent of people worldwide and is the biggest contributor to long-term disability in the general population. Yet only about half of patients respond well to existing treatments.
"The new genetic variants discovered have the potential to revitalise depression treatment by opening up avenues for the discovery of new and improved therapies," said Gerome Breen of King's College London, who worked on the research team.
The study, published on Thursday in the journal Nature Genetics, was a global effort, with data covering more than 135,000 patients with major depression and around 344,000 controls as comparisons.
"This study has shed a bright light on the genetic basis of depression, but it is only the first step," said Cathryn Lewis, another King's College London expert who worked on the team.
"We need further research to uncover more of the genetic underpinnings, and to understand how genetics and environmental stressors work together to increase risk of depression."