Objective: The aim of this study is to identify new genetic variants that cause or predispose to Parkinson’s disease (PD). Our secondary aim is to identify new families where both affected and unaffected individuals are prepared to participate in neurogenetics research.

Background: There are currently 9 well-validated Mendelian genes that have been linked to PD; however the cause of PD is still unknown in approximately 90% of cases with early onset or familial PD. The Parkinson’s Families Project (PFP) recruits familial and early onset PD patients and their unaffected relatives for genetic and linkage analysis, including whole exome sequencing and single nucleotide polymorphism (SNP) array genotyping. PFP is closely linked to the Tracking Parkinson’s PRoBaND study and uses the same detailed clinical assessments.

Methods: 37 hospitals around the UK are recruiting to this study. Clinical data is collected on motor symptoms using the MDS-UPDRS, cognitive symptoms using the Montreal Cognitive Assessment and other non-motor symptoms using standardised questionnaires. DNA samples are extracted from blood or saliva, and genotyped using the LRRK2 KASPR assay, NeuroChip SNP array, exome sequencing, and Multiplex Ligation-dependent Probe Amplification (MLPA).

Results: 547 participants have been recruited as of March 2018. Of these 455 are index cases in the family, 26 are affected relatives and 62 are unaffected relatives (4 unknown). Of the index cases, 131 meet criteria for early onset PD (age of onset ≤ 45), 222 meet criteria for familial PD, and 57 meet both criteria (data missing for 45 patients). So far, 156 patients have been genotyped using the LRRK2 KASPR assay, of which 5.8% were positive for the LRRK2 G2019S mutation. 282 samples have been genotyped using the NeuroChip SNP array; 41 samples with whole exome sequencing and 35 samples with MLPA. So far, we have identified 5.7% of patients carrying a pathogenic mutation out of 296 screened with at least one of the above methods.

Conclusions: A large proportion of PD patients do not have a known genetic mutation, pointing to polygenic or oligogenic inheritance or as yet unidentified single genes. Thorough genetic screening and linkage analysis of affected and unaffected family members is needed to identify new candidate variants.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-parkinsons-families-project-a-family-based-study-of-early-onset-and-familial-parkinsons-disease/