Session Information
Date: Monday, June 20, 2016
Session Title: Epidemiology
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: We investigated whether a genetic risk score for Parkinson’s disease (PD) is associated with the risk of incident PD, and whether the risk score improves prediction of PD. We also studied whether the risk score is associated with basic activities of daily living (BADL) in healthy individuals.
Background: Recent genome-wide association studies have identified 28 independent risk variants for PD, but their clinical relevance remains unknown.
Methods: Within the population-based Rotterdam Study, we genotyped 26 independent genetic risk variants for PD and constructed a genetic risk score in 7167 participants who were free of parkinsonism and dementia at baseline (1990 or 2000). Participants were followed for a maximum of twenty years for the onset of parkinsonism, dementia or death until January 1, 2011 (median follow-up 12.1 years). We used cox proportional hazard models and C-statistics to study the relationship between the genetic risk score and incident PD, adding the risk score to age, sex, smoking and parental history. In an independent sample of 2997 persons free of parkinsonism and dementia, we studied whether the PD risk genes were associated with impaired BADL.
Results: The genetic risk score was associated with incident PD (hazard ratio per standard deviation risk 1.25 [95% confidence interval=1.02;1.55]), but did not substantially improve prediction (change in C=0.01 [-0.011;0.03]).
| HR (95% CI) | C-statistic (95% CI) | |
| Model I | 0.659 (0.599; 0.720) | |
| Age | 1.05 (1.03; 1.07) | |
| Female | 0.66 (0.44; 0.98) | |
| Model II | 0.687 (0.628; 0.745) | |
| Age | 1.05 (1.03; 1.07) | |
| Female | 0.48 (0.30; 0.76) | |
| Smoking (past) | 0.57 (0.35; 0.94) | |
| Smoking (current) | 0.36 (0.18; 0.70) | |
| ≥ 1 parent with PD | 1.29 (0.40; 4.15) | |
| Model III | 0.698 (0.635; 0.760) | |
| Age | 1.05 (1.02; 1.07) | |
| Female | 0.48 (0.30; 0.76) | |
| Smoking (past) | 0.57 (0.35; 0.93) | |
| Smoking (current) | 0.36 (0.19; 0.71) | |
| ≥ 1 parent with PD | 1.25 (0.39; 4.03) | |
| Genetic risk score | 1.25 (1.02; 1.55) |
| BADL | N (%) | OR (95%CI) | P value |
| No impairment | 461 (15.4) | 1.000 (reference) | |
| Any impairment | 2536 (84.6) | 1.110 (1.002; 1.230) | 0.047 |
| Mild impairment | 2017 (67.3) | 1.123 (1.013; 1.246) | 0.028 |
| Moderate to severe impairment | 519 (17.3) | 1.020 (0.889; 1.171) | 0.777 |
Conclusions: Genetic variants for PD are associated with the risk of incident PD in the general population and with impairment in daily functioning in individuals without clinical parkinsonism, but do not improve the clinical prediction of PD.
(Still to be confirmed: 68th AAN Annual Meeting; April 15-21, 2016; Vancouver Convention Centre, Vancouver, BC, Canada). KEYWORDS: Parkinson’s disease, Genetic association study, Prediction, Epidemiology (none of these key words were listed in the next screen).
To cite this abstract in AMA style:
S. Darweesh, V. Verlinden, H. Adams, A. Uitterlinden, A. Hofman, B. Stricker, C. van Duijn, P. Koudstaal, M.A. Ikram. Genetic risk of Parkinson’s disease in the general population [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/genetic-risk-of-parkinsons-disease-in-the-general-population/. Accessed November 22, 2024.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-risk-of-parkinsons-disease-in-the-general-population/