World’s largest study on genetic risk factors for depression will recruit 20,000 women – VCU News


A team of researchers will lead the largest population study of its kind to learn more about genetic variations that affect the risk of depression in individuals after receiving a five-year, $ 8.98 million grant from the National Institute of Mental Health, which is part of the National Institute of Mental Health. Institutes of Health.

The study, “Identifying the Genetic Causes of Depression in a Deeply Phenotyped Population of South Korea”, will focus on deep phenotyping – examining the full picture of all clinical features and symptoms and numerous environmental risk factors disease or illness. – determine which specific genetic factors could underlie major depressive disorder in all its forms. The study will also create the largest available dataset of genetic information related to major depressive disorder for people in East Asia, increasing the diversity of genetic discovery efforts.

Kenneth S. Kendler, MD, professor and distinguished researcher at the Virginia Institute for Psychiatric and Behavioral Genetics at Virginia Commonwealth University and professor in the Department of Psychiatry at VCU School of Medicine, is one of three principal investigators who will lead the study. , which Kendler describes as the “largest deeply phenotypic depression study ever funded,” alongside researchers at the University of California at Los Angeles and Seoul National University Hospital.

The study teams will interview 20,000 women in South Korea – 10,000 with recurrent major depression and 10,000 in the control group – for this project. To keep the sample as homogeneous as possible, Kendler said, the study will include women who have had at least two episodes of major depression and who have no history of drug or alcohol abuse.

“Depression is a complex disease with many factors, and we need large-scale projects to encompass that complexity to give us a real chance to reach the underlying causes of major depressive disorder,” Kendler said. “Having a sample of this size allows us to more precisely determine the factors that influence the manifestation of depression. “

With the work this team is doing to understand the causes of major depressive disorder, Kendler hopes that decades into the future, scientists may have a way to address the biological mechanisms that cause major depression.

“There is certainly hope in the long term, and there are already efforts in this direction to try to develop molecular genetic tests that can indicate with increasing precision a person’s vulnerability to major depression,” Kendler said. “This [study] would contribute substantially to this effort.

Kenneth S. Kendler, MD

The project’s principal investigator, Jonathan Flint, MD, of UCLA’s David Geffen School of Medicine, received nearly $ 9 million for the study, with most of the funding going to Korea for the first four years. to support data collection. . Kendler’s team will receive over $ 535,000 for the VCU site.

Kendler and his team will facilitate the training of researchers, led by Kyoo-Seob Ha, MD, Ph.D., based at the Seoul National University Hospital sites in South Korea to help teach a rigorous protocol for interviewing patients. thousands of study participants around this topic. Flint’s team at UCLA will oversee genotyping efforts and work with the VCU and Korean teams to perform statistical analysis and disseminate the results in scientific papers.

Kendler, one of the world’s most cited psychiatrists known for his international population studies of mental health disorders, and Flint have worked together for more than two decades on projects of this nature. The number of study participants in South Korea is almost double the size of a study they conducted on depression in a deeply phenotyped population over the past decade in China. This project, centered on the China, Oxford and VCU Experimental Research on Genetic Epidemiology (CONVERGE) consortium, was a study of 12,000 participants – 6,000 with depression – to identify the genetic factors of depression. Through this work, the group identified two genetic markers of major depression, publishing articles on the subject in Nature, JAMA Psychiatry and the American Journal of Psychiatry.

“In CONVERGE, we found genetic risks that seemed to be important only in people who had really had very few environmental risk factors for depression in their lifetime, while other types of genetic factors were more important in women developing depression who had experienced quite a lot of adversity – whether in childhood with physical or sexual abuse or in adulthood with traumatic life events, “said Kendler. “We are trying to examine the link between stressful life events and the development [of depression] overtime. This is really about the etiology of major depression using these powerful molecular tools as a way to solve this problem. “

“Depression is a complex disease with many factors, and we need large-scale projects to encompass this complexity to give us a real chance to reach the underlying causes of major depressive disorder.”

Kenneth S. Kendler, MD

Depression affects 10 to 15 percent of the world’s population, Kendler said, and is one of the leading causes of disability around the world, according to the World Health Organization. To determine the causes of this disease, Kendler and his team are trying to understand the genetic and environmental risks as well as the interactions between them.

The research team will ask participants detailed questions about their symptoms of depression, such as changes in mood, sleep or appetite, incidence of anxiety or panic, and history of stress or abuse, and how often they had it, Kendler said.

“We dig deep to try to get it, not just the ‘yes’ [or] “No,” Kendler said, “but a lot of the hallmarks of the complexity of this major depression syndrome. “

Not only is the project an opportunity to contribute to scientists’ knowledge of the causes of major depression, which will help researchers develop more effective tests and treatments for the disease, but it is also an opportunity to diversify image of the genetic research that exists on risk factors for depression in people who are not of European descent. A 2019 article published in Cell by Roseann E. Peterson, Ph.D., VCU co-investigator who will focus on statistical genetic analysis for the latest project in South Korea, revealed the need for more diversity in genome-wide association studies to find the possible causes and treatments of diseases.

“Without global representation in genetic studies, precision medicine efforts will be limited because we do not study the full spectrum of human genetic diversity. It is both a scientific and ethical imperative that we expand study populations to improve understanding of disease in all populations, ”said Peterson, assistant professor of psychiatry at the Virginia Institute for Psychiatric and Behavioral Genetics at VCU. “A study of this size will help us bring together some of this data to identify the genetic factors of depression and can help us determine the causes of the disease to develop appropriate prevention and treatment across the board. “

Along with other population-based research projects already underway at VCU, this new investigation by Flint, Ha and Kendler into major depression in South Korea will increase the available knowledge about disease risks in people of origin. East Asian, an important step towards making medicine more precise, said Peter Buckley, MD, dean of the VCU School of Medicine.

“This project is one of the many ways our researchers are filling the gaps that must be filled to make precision medicine truly possible, helping us meet the unique needs of all patients, regardless of their ancestral origins,” said Buckley. Dr. Kendler and Dr. Peterson’s study will provide crucial data needed to identify the risks associated with major depressive disorder and hopefully lead to improvements in diagnosis and treatment for people around the world.


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