SU researchers help with genetic study about bipolar disorder

Stellenbosch University researchers have played their part in what is said to be the largest genetic study on bipolar disorder to date. Results emanating from the efforts of the international Psychiatric Genomics Consortium of which they are part were recently published in the eminent science publication Nature. Researchers within the study identified 64 regions or genetic markers of the human genome that contain DNA variations that increase a person’s risk of bipolar disorder. This is more than double the number of DNA variations previously identified. The study also found an overlap in the genetic bases of bipolar disorder and other psychiatric disorders, and found that sleep habits and the use of alcohol and other substances play a role in its development.

The Consortium, comprising of an international team of more than 800 researchers, from more than 150 institutions in over 40 countries, was set up to help understand the underlying biology of bipolar disorder and other mental health issues better. According to a press release by the Mount Sinai Hospital in the US, conclusions in the recent study were drawn based on the scanning of 7.5 million common variations in the DNA sequence of nearly 415,000 people. Of these, more than 40,000 had bipolar disorder.

The co-directors of the SA MRC Unit on Risk and Resilience in Mental Disorders, Prof Christine Lochner of the SU Department of Psychiatry, and Prof Dan Stein of the Department of Psychiatry at the University of Cape Town, as well as Dr Nathaniel McGregor of the Human and Systems Genetics working group in the SU Department of Genetics are members of the Consortium.

They have been providing clinical data and preparing DNA samples for genome-wide association studies from the African continent over the last 10 to 15 years, and contributed to the recently published paper. The study was led by Prof Niamh Mullins of the Icahn School of Medicine at Mount Sinai Hospital in the USA.

According to Prof Lochner, who is a clinical psychologist by training, bipolar disorder is a complex psychiatric disorder characterized by recurrent episodes of severely high and low mood and affects an estimated 40 to 50 million people worldwide. It typically begins in young adulthood, often takes a chronic course, and carries an increased risk of suicide, making it a major public health concern and cause of global disability.

According to the release, the biological insights gained from this research could ultimately lead to the development of new and improved treatments or precision medicine approaches to stratify patients at high genetic risk who may benefit from targeted treatment or intervention strategies. Understanding causal risk could aid clinical decision-making in the prevention or management of the illness. Future genetic studies in larger and more diverse populations will have to be done to pinpoint the genes relevant to risk of bipolar disorder in other areas of the genome.

“It is notoriously difficult to find true genetic associations with mental health disorders due to their complex nature. Bipolar disorder has been particularly elusive,” Stellenbosch University geneticist Dr Nathaniel McGregor of the Department of Genetics in the Faculty of AgriSciences adds.

About the value of the Psychiatric Genomics Consortium, he says: “It meets the demand for very large cohort sizes, which are necessary to find genetic associations in complex disorders, such as the psychiatric disorders. In addition to the need for large cohorts, participants comprising genomes representing large genetic diversity are also important in finding true associations.”

Dr McGregor adds: “The inclusion of South African and African populations means better translatability of findings.”

He says South Africa, and the African content, have high prevalence rates of psychiatric disorders, yet relatively low investment in terms of the country’s gross domestic product (GDP).

“Studies such as these advance our understanding of the underlying molecular mechanisms that contribute towards disease manifestation, and therefore bring us closer to potential novel therapeutic targets as well as candidates for functional investigations.”

"This research would not have been possible without the collaborative efforts of scientists worldwide that enabled the study of hundreds of thousands of DNA sequences," said Prof Ole Andreassen, a professor of psychiatry at the Oslo University Hospital. "Through this work, we prioritized some specific genes and DNA variations which can now be followed up in laboratory experiments to better understand the biological mechanisms through which they act to increase risk of bipolar disorder."


  • The SU researchers also contributed to a recent publication emanating from the Psychiatric Genomics Consortium. Their paper in Transactional Psychiatry identified two genetic markers or variants that are associated with some children portraying obsessive compulsive traits.