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

Parkinson's disease, a neurological disorder impacting millions globally, has posed a longstanding puzzle for scientists investigating its genetic origins, particularly within underrepresented populations.

However, a recent pioneering study, outlined in a publication in Nature Genetics, has given fresh insights into this intricate condition through a worldwide collaborative endeavor. This effort was led by co-principal investigator Assistant Professor Foo Jia Nee from LKCMedicine, with co-first author Research Associate Michelle Lian. Professor Tan Eng King, Deputy Chief Executive Officer (Academic Affairs) at the National Neuroscience Institute, stands as a key collaborator representing Singapore in this research initiative.

The Global Parkinson’s Genetics Program (GP2) enlisted the collaboration of at least 16 research centres and organisations spanning Singapore, Peru, the United States, and the United Kingdom for this study. It marks the most extensive investigation into Parkinson's disease genetics to date, with the Singapore team taking the lead in Asia.

Unlike prior studies that often focused solely on European populations, this research involved a diverse cohort of 49,049 Parkinson's disease patients from European, East Asian, Latino, and African backgrounds. This inclusive approach led to the identification of 12 new risk loci, offering valuable insights into the biology of Parkinson’s disease. Furthermore, it revealed genetic distinctions among these four ancestry groups, aiding in the precise mapping of six previously identified Parkinson’s disease loci. Loci denote regions of the genome housing a gene and a DNA sequence variant influencing an individual's disease risk.

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.”