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44 Genetic Risk Factors Identified for Major Depression

A global research project has mapped out the genetic basis of major depression, identifying 44 genetic variants which are risk factors for depression, 30 of which are newly discovered. The study, by the Psychiatric Genomics Consortium, and co-led in the UK by King's College London, is the largest study to-date of genetic risk factors for major depression. Published online on April 26, 2018 in Nature Genetics, the research finds that the genetic basis for major depression is shared with other psychiatric disorders such as schizophrenia, and that all humans carry at least some of the 44 genetic risk factors identified in the study. The article is titled “Genome-Wide Association Analyses Identify 44 Risk Variants and Refine the Genetic Architecture of Major Depression.” A significant number of the genetic variants identified in the study are directly linked to the targets of current antidepressant medications. Analysis of the data also suggests that having a higher body mass index (BMI) is linked to an increased risk of major depression. Previous studies have struggled to identify more than a handful of genetic variants associated with depression. By combining seven separate datasets, the research team included data on more than 135,000 people with major depression and more than 344,000 controls. The study was an unprecedented global effort by over 200 scientists who work with the Psychiatric Genomics Consortium, and was led by the University of North Carolina School of Medicine and the University of Queensland in Australia. Professor Cathryn Lewis and Dr. Gerome Breen of King's College London led the UK contribution, along with scientists and psychiatrists from the Universities of Edinburgh, Cardiff, and University College London (UCL). The authors found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: namely, that lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology.

“With this study, depression genetics has advanced to the forefront of genetic discovery,” says Dr. Breen from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London. “The new genetic variants discovered have the potential to revitalize depression treatment by opening up avenues for the discovery of new and improved therapies."

Major depression affects approximately 14% of the global population and is the biggest contributor to long-term disability in the general population worldwide. Yet only about half of patients respond well to existing treatments.

“Depression is an incredibly common disorder that affects millions of people in the UK,” says Professor Lewis of the IoPPN, who is leading efforts to conduct even larger international studies.

“This study has shed a bright light on the genetic basis of depression, but it is only the first step,” added Professor Lewis. '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.”

Dr. Breen, with other scientists, is currently working on an online tool, for release in the autumn, to allow volunteers with depression to take part in further genetic studies. Members of the public who want to be notified about the launch of the study can email darr@kcl.ac.uk.

[Press release] [Nature Genetics abstract]