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The genetics of Parkinson's disease: Progress and therapeutic implications


  • Funding agencies: This work was supported, in part, by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services (project no.: Z01 AG000949-06). This study was supported by grants from the “Internationaal Parkinson Fonds,” The Netherlands, and the Netherlands Organization for Scientific Research (NWO, VIDI grant; to V.B.).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

Correspondence to: Dr. Andrew B. Singleton, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A1014, 35 Convent Drive, Bethesda, Maryland 20892, USA;


The past 15 years has witnessed tremendous progress in our understanding of the genetic basis for Parkinson's disease (PD). Notably, whereas most mutations, such as those in SNCA, PINK1, PARK2, PARK7, PLA2G6, FBXO7, and ATP13A2, are a rare cause of disease, one particular mutation in LRRK2 has been found to be common in certain populations. There has been considerable progress in finding risk loci. To date, approximately 16 such loci exist; notably, some of these overlap with the genes known to contain disease-causing mutations. The identification of risk alleles has relied mostly on the application of revolutionary technologies; likewise, second-generation sequencing methods have facilitated the identification of new mutations in PD. These methods will continue to provide novel insights into PD. The utility of genetics in therapeutics relies primarily on leveraging findings to understand the pathogenesis of PD. Much of the investigation into the biology underlying PD has used these findings to define a pathway, or pathways, to pathogenesis by trying to fit disparate genetic defects onto the same network. This work has had some success, particularly in the context of monogenic disease, and is beginning to provide clues about potential therapeutic targets. Approaches toward therapies are also being provided more directly by genetics, notably by the reduction and clearance of alpha-synuclein and inhibition of Lrrk2 kinase activity. We believe this has been an exciting, productive time for PD genetics and, furthermore, that genetics will continue to drive the etiologic understanding and etiology-based therapeutic approaches in this disease. © 2013 Movement Disorder Society