Objective: (i) To describe the demographic, clinical and genetic features of a large cohort of familial autosomal dominant Parkinson’s disease (PD) patients in the UK.

(ii) To outline the planned future analysis for identification of novel loci and genes that cause PD.

Background: Identification of causative genetic variants in autosomal dominant Parkinson’s disease (ADPD) have led to novel insight into the biology of PD. Families with greater numbers of affected individuals are more likely to harbour a genetic cause.

Method: Participants with PD and having at least 3 affected family members were recruited from three large studies: the Parkinson’s Families Project (PFP), The Clinical Neurological Disease Biobank and Neurogenetics Study (CANDAS) Biobank, and the Parkinson’s UK Tracking Parkinson’s Study (PRoBaND). Data on participant demographics, clinical state and family structure were collected. DNA was extracted and analysed through a combination of techniques including genotype array (NeuroChip v1 and v1.1, and NeuroBooster Array), whole exome and genome sequencing (Genomics England 100K Genomes and Global Parkinson’s Program [GP2]).

Results: In total 423 participants from 344 families with an average size of 3.3 affected family members were recruited to the ADPD cohort. 374 affected participants with an average age of onset of 56.7 (range 0-86), and 46 unaffected relatives were recruited. 54% were male. 37/344 families have been identified to have causative variants in disease-related genes including LRRK2 (7%), SNCA (1.7%), PRKN (1.2%), PINK1 (0.3%), DJ1 (0.3%), VCP (0.3%).

Conclusion: We have identified a population of participants with PD who have a high a priori likelihood of having a genetic cause for Parkinson’s disease and characterised these individuals. Pseudodominance explains the presence of recessive genes in families with an autosomal dominant structure. Further techniques to explore for causative variants will employ variant sharing analysis, genetic ancestry and geographic mapping. A targeted analysis of genes implicated in known disease pathways is planned.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-uk-wide-effort-for-identification-of-loci-for-autosomal-dominant-parkinsons-disease/