Study Rationale:
The immune system plays a complex role in Parkinson’s disease (PD), sometimes protecting the brain and other times accelerating damage. Two specific families of immune genes (HLA and KIR) are critical to this process, but they are highly variable across people and difficult to read using standard genetic tests. Current research often relies on "guessing" these gene variants based on incomplete data, which is often inaccurate. To fully understand how the immune system affects PD, researchers need a precise method to identify exactly which gene variants a person carries.
Hypothesis:
We propose that applying modern, high-accuracy software to existing genetic sequencing data will create a definitive "dictionary" of immune genes for Parkinson's study participants, revealing connections between the immune system and the disease that prior, less accurate standard methods could have missed.
Study Design:
We will leverage data that has already been collected from thousands of participants in the AMP-PD program rather than recruit new patients. Using powerful cloud computing, we will analyze thousands of existing whole genome sequencing and RNA sequencing files and run several top-tier software programs to determine each individual’s specific HLA and KIR genes. This will generate a high-confidence set of immune gene variants for the research community.
Impact on Diagnosis/Treatment of Parkinson’s disease:
This project will give researchers a free, highly accurate resource to study how specific immune genes influence PD risk, symptom severity, and progression. This could ultimately help doctors predict who is more likely to develop specific symptoms or respond better to certain treatments.
Next Steps for Development:
Upon completion, this detailed genetic database and the methods used to create it will be shared immediately with the global research community. This will enable scientists to begin validating new genetic links to Parkinson's symptoms and explore personalized medicine approaches, such as whether patients with certain HLA gene variants respond better to certain types of therapy.