LKCMedicine team part of global study that reveals new genetic insights into Parkinson’s Disease

Parkinson's disease, a neurological disorder affecting millions worldwide, has long puzzled scientists seeking to understand its genetic roots, especially among underrepresented populations.

However, a recent groundbreaking study, detailed in a paper published in Nature Genetics, has shed new light on this complex condition through a global collaborative effort, which include co-principal investigator LKCMedicine Assistant Professor Foo Jia Nee and co-first author LKCMedicine Research Associate Michelle Lian. Additionally, National Neuroscience Institute Deputy Chief Executive Officer (Academic Affairs) Professor Tan Eng King is one of the main collaborators representing Singapore in this study.

Involving at least sixteen research centres and organisations from Singapore, Peru, the United States and the United Kingdom under the Global Parkinson’s Genetics Program (GP2), this study represents the most extensive exploration of Parkinson's disease genetics to date, with the team in Singapore leading the collaborative efforts in Asia.

Unlike previous studies that often focus on European populations or a single ancestry, this research pooled data from 49,049 patients with Parkinson's disease from European, East Asian, Latino and African descent. This approach revealed 12 new risk loci, providing valuable insights into Parkinson’s disease biology. It also identified genetic differences between these four ancestry groups that helped the team to ‘fine-map’ six previously identified Parkinson’s disease loci. Loci are regions of the genome that harbour a gene and a DNA sequence variant that alters disease risk of an individual.

Analyses carried out in the multi-ancestry study. Photo Credit: Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

‘Fine-mapping’ narrows down the possible genomic region harbouring the gene that plays a direct role in the specific functions in patients’ bodies that are affected in a disease. These can then be investigated as potential drug targets, alongside genes in the 12 newly identified loci that may also play such a role.  

Ms Lian emphasised the significance of recognising both the similarities and differences in genetic risk factors across ancestries.  She said, “This finding highlights the importance of considering genetic diversity when studying complex diseases like Parkinson's which can lead to development of personalised treatments for better outcomes.”

(From left) Research Associate Michelle Lian and Assistant Professor Foo Jia Nee reviewing Asian population data for the study.

“What is significant is that the genetic variants identified in this study can also be leveraged to calculate an ancestry-specific polygenic risk score — a personalised metric estimating an individual's likelihood of developing Parkinson's disease. Using this information, healthcare professionals can identify individuals who are at heightened risk of developing Parkinson’s disease and take action through tailored monitoring and early intervention, including participation in neuroprotection trials,” explained Prof Tan.

While polygenic risk scores calculated from European-ancestry studies can already be used to predict Parkinson’s disease risk in Singapore or East Asian population, the risk prediction will be considerably more accurate if an East Asian- or Asian-specific score is calculated, using the new knowledge gained on ancestry similarities and differences in this study. The discovery of the 12 new loci also adds to the improved accuracy of this risk prediction.

This study demonstrates the power of global collaboration to advance science, and the importance of including more non-European participants. The number of European participants (39,275) in this study is more than five times bigger than the number of East Asian participants (7,046), which is the second largest group in the study. Without sufficient numbers, it is difficult to study the differences between ancestries in finer detail.

Asst Prof Foo added, “Moving forward, we need to further increase the number of non-European participants by expanding the collaborative network globally. This multi-ancestry project is a blueprint for large-scale genetic research to better understand Parkinson’s Disease. There is immense promise for more targeted and personalised risk prediction, treatment and prevention for Parkinson’s Disease. But this can only be realised if there is broader interest and participation from other researchers across Asia.”