Global Study Examines Parkinson’s Genes To Support Precision Therapies

Researchers from the Institute of Neurogenetics publish new findings on the genetic diversity of Parkinson's disease in the journal Lancet Neurology.

An international research team led by Dr. Lara M. Lange and Prof. Dr. Christine Klein from the Institute of Neurogenetics at the University of Lübeck has presented the largest genetic study on Parkinson's disease to date as part of the "Global Parkinson's Genetics Program" (GP2). The study, published in the journal The Lancet Neurology, uses data from eleven population groups worldwide to show that disease-causing genetic alterations occur with very different frequencies depending on origin. This has implications for who can already benefit from new therapies. 

Parkinson's disease is the second most common neurodegenerative disease worldwide after Alzheimer's and, according to the World Health Organization, is among the fastest-growing neurological diseases. However, genetic research on the disease has so far focused almost exclusively on people of European descent. This is problematic because the genetic causes of the disease depend heavily on a person's ethnic origin.

This work is part of the Global Parkinson's Genetics Program (GP2), an international consortium that pools genetic data from people with Parkinson's disease worldwide to advance diagnostics and precision medicine. "GP2 enables the inclusion of numerous cohorts from different regions of the world, thus providing an unprecedented breadth and depth of genetic analyses," explains Prof. Dr. Christine Klein, emphasizing: "Without the close collaboration with the numerous GP2 partner centers and their cohorts, a study of this size and diversity would not have been possible."

Large regional differences in the frequency of gene variants

The focus is on two genes, GBA1 and LRRK2, which are already targets of new drugs. Both provide instructions for building enzymes responsible for the "waste disposal" of waste products in nerve cells. If these enzymes malfunction, harmful protein deposits can accumulate and thus lead to the development of Parkinson's disease. The study shows that while these genes are important worldwide, the specific changes that occur and where they occur vary considerably from region to region.

Why this matters to those affected

For the study, the team analyzed genetic data from nearly 100,000 people from eleven regions of the world. Almost a third of these participants came from populations that have been largely overlooked in previous research, such as those in Africa, Latin America, and Asia. The findings have immediate implications, because if genetic diagnostics are focused solely on variants known in Europe, the causes of disease in people from other regions often remain undiscovered. Consequently, they also fall through the cracks when it comes to new, genetically targeted therapies – which, to date, have been tested almost exclusively in Europe and North America.

“Our study is an important first step towards truly global precision medicine for Parkinson’s disease. Before we can make genetically targeted therapies available worldwide, we need to understand which genetic causes play a role in different populations and where potentially suitable patients for future genetically stratified clinical trials are located,” adds Dr. Lara M. Lange.

Lübeck participation

Data from Lübeck's own patient cohorts were incorporated into the analyses. Furthermore, Prof. Klein from the Institute of Neurogenetics leads the Monogenic Network within GP2, which enabled the inclusion of genetically well-characterized Parkinson's cases from numerous international cohorts in the study. Dr. Lange, as a postdoctoral researcher at the Institute of Neurogenetics in Lübeck, played a key role in establishing this Monogenic Network and significantly shaped its structure and scientific focus. GP2 and the large number of participating cohorts thus form the basis for the study's ability to reveal the genetic diversity of Parkinson's disease across eleven population groups.