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Uncovering the genetic basis of major depression

Major Depressive Disorder (MDD) is an important and persistent public health issue. The biological mechanisms underlying MDD are poorly understood, despite an estimated 40% genetic basis, due to the complex nature of the disorder.

As part of the Psychiatric Genomics Consortium, a group of over 200 scientists contributed to a multinational, genome-wide association study seeking to identify genetic variants underlying major depression. Using an estimated 135,000 patients with major depression and 344,000 controls, they found 44 genetic variants (loci) with a statistically significant association with depression, 30 of these newly-discovered, and 153 genes. Published on April 26 in Nature Genetics, this study is unique in that it used a very large sample size to overcome genetic heterogeneity and pinpoint risk alleles.

Evidence for overlap between the genetic basis of depression and other psychiatric disorders was also presented, with 6 shared loci identified between depression and schizophrenia. Measures of sleep quality (e.g. insomnia and tiredness) and obesity were further found to have common genetic underpinnings with depression.

The ultimate aim of this research is to bring precision medicine to psychiatry. Knowing which genetic variants are contributing to patients’ depression could lead to a more accurate diagnosis at first presentation, including predicting the risk of recurrence and poor treatment response as well as the likelihood of developing a related psychiatric disorder. Understanding the genetic basis of depression should further support the development of new antidepressant medications and improvement of current therapies to better patient outcomes.

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