VCU researchers, international partners first to identify risk genes for clinical depression

vcu-logoFor the first time in scientific history, researchers have identified specific genetic clues to the underlying etiology of clinical depression. The findings are the result of an international collaboration among researchers from Virginia Commonwealth University, the University of Oxford and throughout China to localize risk genes for major depressive disorder.

While prior studies have failed to identify replicated evidence for molecular genetic markers that predispose to risk for the disease, the international research team, in which VCU’s Virginia Institute for Psychiatric and Behavioral Genetics was a key participant, successfully isolated individual changes in DNA that increase risk for major depression.

The study, “Sparse Whole-Genome Sequencing Identifies Two Loci for Major Depressive Disorder,” was published as an advanced online publication in the journal Nature on July 15.

“This report shows for the first time that genome-wide association studies – a method that has found risk genes from many important complex human disorders – can work for major depression,” said joint-senior author Kenneth S. Kendler, M.D., professor of psychiatry and human and molecular genetics at VCU School of Medicine. “With these genome-wide studies, as you identify more markers your ability to identify specific biological pathways to illness substantially improves.”

According to the World Health Organization, clinical depression carries the second heaviest burden of disability among all medical conditions worldwide and accounts for more than 8 percent of all U.S. years lived with disability. The findings from this study could potentially lead to new ways to predict risk for depression and treatments for the disease.

“Each one of these molecular genetic findings opens a potential biological pathway that could lead to the development of new treatments, which have not yet been conceived because of our lack of understanding of the biology of the disease,” Kendler said, adding that the findings also provide the potential to be able to assess people’s genetic vulnerability for inheriting the disease.

Major depression is one of the most common mental disorders in the U.S., according to the National Institute of Mental Health. In 2012, an estimated 16 million adults in the U.S. aged 18 or older had at least one major depressive episode in the past year, representing almost 7 percent of the population.

Kendler attributes the research’s success to the carefully designed study sample, which consisted of 5,303 Chinese women with recurrent major depression from 58 hospitals throughout China and 5,337 Chinese women in the control group. The study was limited to women because about 45 percent of the genetic liability to major depressive disorder is not shared between sexes. The women with depression in the study had to be at least 30 years old; have had two episodes of major depression; had no history of alcohol or drug abuse, bipolar illness, or psychosis; and have had all four grandparents of Han Chinese descent.

“It is likely that our study was successful because the patients we studied were relatively homogenous and severely ill,” Kendler said.

Key collaborators involved in this study included Jonathan Flint, Ph.D., professor, Wellcome Trust Centre for Human Genetics at the University of Oxford, and Jun Wang, Ph.D., from the Beijing Genomics Institute.

Along with Flint, Kendler hopes to return to China in the near future to collect another 48,000 samples, which they expect will replicate and substantially extend the Nature journal study findings.

“If our calculations are correct, the additional 48,000 samples will produce a substantial number of new findings, which will greatly improve the ability for us to scientifically understand the underlying biology that predisposes to major depression,” Kendler said.

Work conducted at the VCU Virginia Institute for Psychiatric and Behavioral Genetics was supported by a grant from the U.S. National Institute of Mental Health, grant number MH100549, and by London-based biomedical research charity the Wellcome Trust.

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