A global study of nearly one hundred thousand people reveals how Parkinson's genetic risks vary across eleven different world regions

A massive international research effort has created the first comprehensive map of how the genetic factors linked to Parkinson's vary across eleven different global populations. This study, published in The Lancet Neurology journal, analysed genetic data from nearly one hundred thousand individuals. Led by the Global Parkinson's Genetics Program, known as GP2, the research marks a crucial shift in medical science because almost a third of the participants came from ancestries that have historically been overlooked in genetic research, including people of African, East Asian, South Asian, Central Asian, and Latin American descent. Historically, genetic studies of the condition have focused almost exclusively on people of European ancestry. This narrow focus has created a major gap in understanding because the genetic variations that cause or increase the risk of developing Parkinson's can differ wildly depending on where a person's ancestors came from. Because of this, genetic tests designed for European populations often fail to detect the causes of the condition in individuals from other backgrounds, meaning they could miss out on emerging, transformative therapies. The international team of scientists focused their attention on two specific genes, named GBA1 and LRRK2. Both of these genes provide instructions for cells to make enzymes that clear out waste inside nerve cells. When these enzymes do not work properly, toxic proteins build up and damage the brain. Researchers are already testing new treatments that target these precise genetic pathways, making it vital to know who actually carries these variants. The results showed that while these two genes are relevant across the entire world, the exact variants and how common they are change dramatically from region to region. For example, only about two per cent of all people with the condition in the study carried a direct, causative variant, but this rate ranged from less than half a per cent in African and Central Asian populations to more than ten per cent in Middle Eastern and Ashkenazi Jewish populations. When looking at broader risk variants within the same genes, GBA1 variants were found to be the most common globally, but they showed immense diversity. In contrast, East Asian populations were much more likely to carry risk variants on the LRRK2 gene, such as the variants known as R1628P and G2385R, which are rarely seen in other groups. Currently, almost all clinical trials for genetically targeted treatments are taking place in Europe and North America. This study highlights a pressing need to diversify these trials and genetic testing globally. Without this global approach, researchers warn that emerging precision medicines may only benefit a small fraction of the global population. By mapping these genetic differences, the team hopes to ensure that future treatments can be tailored to individuals around the world, making healthcare fairer and more effective for everyone living with the condition.