Objective: ROPAD is an international, multicenter, epidemiological study that aims at a better understanding of the contribution of genetics to Parkinson’s disease (PD) based on analyzing 10,000 individuals, which are recruited in a standardized manner.

Background: PD had long been considered a largely non-genetic disorder. Recent discoveries, however, suggest the existence of numerous monogenic forms. One of these is LRRK2-associated PD, which is inherited in an autosomal dominant manner with incomplete penetrance. Additionally, certain variants in GBA increase the risk of developing PD. The overall contribution of these genetic factors to PD is only beginning to be understood.

Method: ROPAD enrolls: (A) patients that have received a clinical diagnosis of PD, (B) family members of PD patients, who have had a positive genetic finding in the LRRK2 gene, and (C) individuals that are at increased risk of developing PD due to being of Ashkenazi Jewish or North African descent. ROPAD’s three-step genetic analytic strategy includes (1) an initial screening for LRRK2 hotspot variants and for variants in the whole GBA gene, (2) a PD gene panel following negativity of step 1, and (3) whole genome sequencing of selected patients (early onset; family history; negative in steps 1 and 2).

Results: Within the first eight months of the study, 1,360 individuals from 30 centers (eight countries) were enrolled. The following preliminary results focus on the 1,288 individuals that currently represent cohort A (see Methods): 1,232 PD patients were whites (95.7%), 793 were male (61.6%), 353 had a positive family history (27.4%), and 1,126 were on L-Dopa treatment at the time of inclusion (87.4%). Mean age at disease onset was 60.2 (+/- 11.5) years, while mean age at inclusion was 67.0 (+/-10.4) years. Steps 1 and 2 of the genetic analysis have been completed for 1,288 patients (100%) and 806 patients (62.6%), respectively. A GBA risk factor was identified in 110 patients. Forty-five patients were diagnosed with LRRK2-associated PD, ten with PRKN-associated PD, and an additional six patients with six distinct other genetic forms of PD.

Conclusion: Extrapolating from the current data, we estimate ~14% of ROPAD participants to receive a positive genetic testing report. ROPAD can thereby be expected to enable valuable novel insights into the role of genetics in PD.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/the-ropad-rostock-international-parkinsons-disease-study-study-towards-defining-the-genetic-epidemiology-of-the-disease/