| Title: |
Polygenic Risk Score Combined with Transcranial Sonography Refines Parkinson's Disease Risk Prediction |
| Authors: |
Kals, Mart; Reigo, Anu; Teder‐Laving, Maris; Vaht, Mariliis; Nikopensius, Tiit; Metspalu, Andres; Toomsoo, Toomas |
| Contributors: |
Haridus- ja Teadusministeerium; European Regional Development Fund |
| Source: |
Movement Disorders Clinical Practice ; volume 12, issue 7, page 928-937 ; ISSN 2330-1619 2330-1619 |
| Publisher Information: |
Wiley |
| Publication Year: |
2025 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Background Dopaminergic neuron depletion in the substantia nigra (SN) and the pathological aggregation of α‐synuclein are the neuropathological hallmarks of Parkinson's disease (PD). Objectives This study aimed to investigate the association between the polygenic risk score for PD (PD‐PRS) and transcranial sonography (TCS)‐measured SN hyperechogenicity to enhance the accuracy of PD susceptibility prediction. Methods PD‐PRSs were calculated for over 41,000 Estonian Biobank participants age 55+ years without a PD diagnosis. Participants in the highest and lowest PD‐PRS percentiles (n = 222) underwent TCS measurements and Sniffin’ sticks olfactory testing. A multivariable logistic regression model was used to examine the associations between PD‐PRS, risk and prodromal markers, and SN hyperechogenicity. Results Data from 204 participants with TCS measurements were analyzed, including 107 individuals in the high‐risk PD‐PRS group and 97 in the low‐risk PD‐PRS group. Incorporating PD‐PRS group assignment improved the explained variance in SN hyperechogenicity from 17.2% to 31.9%. Participants in the low‐risk PD‐PRS group had 0.16 times lower odds (95% confidence interval (CI) = 0.07–0.35, P < 0.001) of developing SN hyperechogenicity compared to high‐risk PD‐PRS individuals. Each unit increase in the Sniffin’ sticks olfactory test score was significantly associated with reduced odds of SN hyperechogenicity (adjusted odds ratio = 0.60, 95% CI = 0.47–0.78, P = 0.002). Conclusions Our findings indicate that TCS‐measured SN hyperechogenicity is associated with PD‐PRS and olfactory impairment. This combined assessment may improve early diagnosis of prodromal PD by pinpointing individuals at increased risk. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/mdc3.70011 |
| Availability: |
https://doi.org/10.1002/mdc3.70011; https://movementdisorders.onlinelibrary.wiley.com/doi/pdf/10.1002/mdc3.70011 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.C0AE8219 |
| Database: |
BASE |