An Exploratory Study Using Electronic Medical Records to Assess the Feasibility of Establishing Cohorts of Patients with Genetic Causes of Parkinson's Disease

Abstract

Background: More efficient screening methods are needed to improve the ability to identify and follow genetic cohorts in Parkinson's disease (PD).

Objective: To explore the use of the electronic medical records (EMRs) to identify participants with PD.

Methods: Using an algorithm previously developed in collaboration with Maccabi Healthcare Services (MHS), approximately 5,200 participants with PD were identified, more than 3,200 were screened, and 837 participants were enrolled and genotyped for leucine-rich repeat kinase 2 (LRRK2) and beta-glucocerebrosidase (GBA) variants. Questionnaires were completed to ascertain Ashkenazi Jewish (AJ) ancestry and family history of PD.

Results: Among 837 participants with PD, 82% were 65 years and older and 72% had a family history of AJ ancestry. Among those with AJ ancestry, 15.6% reported having relatives with PD. The frequency of observed mutations for LRRK2 and GBA genes combined was approximately 15.4%. The frequency of observed LRRK2 mutation was 6.1% overall and 7.2% from those with AJ ancestry; and for GBA mutation was 9.3% overall and 11.2% from those with AJ ancestry.

Conclusion: Although the frequency of observed mutations in this study was lower than anticipated, mutation carriers were enriched among those with a family history of AJ ancestry increasing nearly 2-3-fold, from 3% -7% (LRRK2) and 4% -11% (GBA). The identification (and selection) of PD patients through EMRs prior to genotyping is a viable approach, to establish a genetically defined cohort of patients with PD for clinical research.

Keywords: Parkinson mutations; Parkinson’s disease; genetic testing; glucocerebrosidase.

Fig. 1

Summary of recruitment to genetic results. Out of 5,200 participants who met the criteria for PD or high probability of PD as identified from the EMR review: 3,218 were contacted and 1,982 were not contacted due to early study completion. More than 2,380 participants out of 3,218 participants contacted either declined, did not meet the study criteria, or failed to meet screening criteria resulting in enrollment of 837 participants. The genetic dataset is shown within the dashed shaded box. Of the 837 participants, a total of 823 participants completed the study, and 14 participants discontinued primarily for not meeting study inclusion eligibility post enrollment (following the issuance of the protocol clarification letter). 788 participants had a definitive or clinically established PD diagnosis as per MDS criteria, and 35 participants whose EMR did not include a clinically established diagnosis of PD, but included high probability or suspected of PD. Among those 788 participants with the clinically established or definitive PD diagnoses, those identified as mutation carriers for LRRK2 and GBA were 48 and 73, respectively. 667 participants were identified as idiopathic PD. At the end of trial more than 96% of the participants (807) consented to receive the genetic results, and 93% (780) of the participants wanted to be re-contacted for future research. Dx, diagnosis; PD, Parkinson’s disease.