Genetic factors play a major role in the development of bipolar disorder. In an effort to better understand the underlying biology, researchers are constantly studying the genetic makeup of people with bipolar disorder. The Psychiatric Genomics Consortium's Genome-Wide Association Study (GWAS) is the largest of its kind. The study analyzes data from ver 150,000 people of European, East Asian, African-American and Latin American descent. The latest results have now been published in the renowned scientific journal “Nature”.
Either manic episodes with lots of energy or the complete opposite: depression and listlessness - this is what the days of people with bipolar disorder can look like. An estimated 40 to 50 million people worldwide are affected. The illness is associated with a number of negative consequences and risks, including an increased risk of suicide. The causes of bipolar disorder are complex and the biology on which it is based is still largely unexplored. What is clear, however, is that a key risk factor for bipolar disorder is a genetic predisposition. Small variants in a large number of genes are responsible for this predisposition.
“The more we know about the biology behind the disorder and the risk factors, the greater the chance of improved diagnosis and treatment options through precision medicine,” explains Prof. Dr. Andreas Forstner from the Institute of Human Genetics at the UKB and shared last author of the study. He is a member of the Transdisciplinary Research Area (TRA) “Life and Health” at the University of Bonn and also works at the Institute of Neuroscience and Medicine (INM-1) at Forschungszentrum Jülich.
The study compared the genes of more than 2.9 million participants, including over 150,000 people with bipolar disorder. The idea behind this is that many people with bipolar disorder have the same genetic variants that are partly responsible for the illness.
New responsible genes discovered
In total, the study identified 298 regions of the genome in which genetic variants increase the risk of bipolar disorder - 267 of which were newly discovered in the current version of GWAS. The study also identified a new region that is associated with an increased risk of bipolar disorder, particularly in samples of East Asian origin. In the identified regions, 36 specific genes are suspected to be relevant for bipolar disorder. The next steps in research could be to investigate these genes in more detail. They could also be used to research new targets for drugs against bipolar disorder.
“In the study, we also found genetic differences between different clinical manifestations of bipolar disorder. This may be important for research into new diagnostic and treatment approaches,” says Prof. Dr. Markus Nöthen, Director of the Institute of Human Genetics at the UKB and co-author of the study. He is a member of the Cluster of Excellence ImmunoSensation2 of the Transdisciplinary Research Area (TRA) “Life and Health” and at the University of Bonn.
“Our results also suggest that different types of nerve cells in the brain play a role in bipolar disorder, and possibly also certain cells outside the brain. This is where further research can start,” adds Friederike David, doctoral student at the University of Bonn's Institute of Human Genetics at the UKB and shared second author of the study.
Funding
The study was conducted by the Psychiatric Genomics Consortium (PGC), an international consortium of researchers investigating the genetics of mental illness. The PGC comprises over 800 researchers from more than 150 institutions in over 40 countries. In German-speaking countries, in addition to the UKB and the University of Bonn, the Central Institute of Mental Health in Mannheim, the University Hospital of Munich, the Department of Psychiatry and Psychotherapy at the University Hospital of Marburg, the Department of Mental Health at the University Hospital of Münster and the University Hospital of Basel were also involved.
The study was funded by the US National Institute of Mental Health, among others.
Publikation
Kevin S. O’Connell et al.: Genomics yields biological and phenotypic insights into bipolar disorder; Nature; DOI: https://doi.org/10.1038/s41586-024-08468-9
Contact
Director of the Institut of Human Genetics
University Hospital Bonn
Phone +49 228 287-51100
E-mail: markus.noethen@uni-bonn.de
