March 3, 2026

@michaelokun

How about a polyexposure score for Parkinson’s? Polyexposure score refers to the 'combining' of many lifetime environmental and internal exposures into one cumulative risk estimate, similar to how a polygenic risk score combines many genetic variants. Okubadejo and colleagues describe in a new paper in Movement Disorders the urgent need to define and operationalize a Parkinson’s disease polyexposure score and to formally integrate the 'exposome' into how we classify and study PD. Key points: – The exposome includes general external factors such as pesticides, solvents and air pollution, individual behaviors such as smoking, caffeine, diet and exercise, and internal biology such as inflammation, diabetes and the microbiome. – Most environmental risk factors for PD have modest effect sizes alone, however combining them into a polyexposure score may improve risk prediction and possibly progression modeling. – The International Parkinson and Movement Disorder Society Clinical and Biological Framework now includes the exposome as a formal tier, signaling that environment and biology must be integrated alongside genetics and biomarkers. My take: We have invested decades decoding the genome. It is time to decode the 'biography' of the person that goes w/ the genes. PD is not just DNA. It is lived exposure across a lifespan. A thoughtful polyexposure score could move us closer to prevention, earlier identification and more personalized care. Here are 5 points that resonated w/ me: 1- Parkinson’s disease risk likely reflects cumulative exposures across decades, not a single toxin or trigger. 2- Pesticides, solvents, head trauma, diabetes, gut inflammation and lifestyle factors may interact w/ genetic susceptibility in complex ways. 3- A well-constructed polyexposure score could eventually help providers identify higher risk folks before motor symptoms emerge. 4- Longitudinal biobanks, multiomics, wearables and geospatial data will be essential to build and validate a meaningful score. 5- Prevention strategies may become more realistic if we can quantify modifiable environmental risks w/ the same rigor we have applied to genetics. #parkinson #michaelokun #fixelinstitute