Polygenic Risk Score Combined with Transcranial Sonography Refines Parkinson's Disease Risk Prediction

Area of Science:

• Neuroscience
• Genetics
• Medical Imaging

Background:

• Parkinson's disease (PD) is characterized by dopaminergic neuron loss in the substantia nigra (SN) and alpha-synuclein aggregation.
• Identifying individuals at high risk for PD is crucial for early intervention.

Purpose of the Study:

• To investigate the association between the polygenic risk score for PD (PD-PRS) and SN hyperechogenicity.
• To assess the potential of combining PD-PRS and SN hyperechogenicity for improved PD susceptibility prediction.

Main Methods:

• Calculated PD-PRS for over 41,000 Estonian Biobank participants aged 55+ without a PD diagnosis.
• Conducted transcranial sonography (TCS) for SN hyperechogenicity and olfactory testing (Sniffin' sticks) in high and low PD-PRS groups.
• Utilized multivariable logistic regression to analyze associations between PD-PRS, risk markers, and SN hyperechogenicity.

Main Results:

• Analyzed data from 204 participants; PD-PRS assignment improved explained variance in SN hyperechogenicity from 17.2% to 31.9%.
• Low PD-PRS group had significantly lower odds of SN hyperechogenicity compared to the high-risk group (OR=0.16, P<0.001).
• Improved olfactory test scores were associated with reduced odds of SN hyperechogenicity (aOR=0.60, P=0.002).

Conclusions:

• TCS-measured SN hyperechogenicity is significantly associated with PD-PRS and olfactory impairment.
• Combined assessment of PD-PRS, SN hyperechogenicity, and olfactory function may enhance early diagnosis of prodromal PD.
• This approach can help identify individuals at increased risk for developing Parkinson's disease.