title: Advances in the genetics of Parkinson disease.
abstract: Parkinson disease (PD) is a multifactorial neurodegenerative disease that was long considered the result of environmental factors. In the past 15 years, however, a genetic aetiology for PD has begun to emerge. Here, we review results from linkage and next-generation sequencing studies of familial parkinsonism, as well as candidate gene and genome-wide association findings in sporadic PD. In these studies, many of the genetic findings overlap, despite different designs and study populations, highlighting novel therapeutic targets. The molecular results delineate a sequence of pathological events whereby deficits in synaptic exocytosis and endocytosis, endosomal trafficking, lysosome-mediated autophagy and mitochondrial maintenance increase susceptibility to PD. These discoveries provide the rationale, molecular insight and research tools to develop neuroprotective and disease-modifying therapies.
authors.affiliation: Department of Medical Genetics, UBC Pavillion Hospital, 2nd floor, Room S-132 Koerner Building, VCHRI, 2211 Wesbrook Mall, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Trinh
authors.forename: Matt
authors.initials: M
authors.lastname: Farrer
mesh_terms: D030541:Databases, Genetic; D059647:Gene-Environment Interaction; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics* / Q000628:therapy