Genetics of Parkinson's disease: the yield

Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1:S35-8. doi: 10.1016/S1353-8020(13)70011-7.


The discovery of genes implicated in familial forms of Parkinson's disease (PD) has provided new insights into the molecular events leading to neurodegeneration. Clinically, patients with genetically determined PD can be difficult to distinguish from those with sporadic PD. Monogenic causes include autosomal dominantly (SNCA, LRRK2, VPS35, EIF4G1) as well as recessively (PARK2, PINK1, DJ-1) inherited mutations. Additional recessive forms of parkinsonism present with atypical signs, including very early disease onset, dystonia, dementia and pyramidal signs. New techniques in the search for phenotype-associated genes (next-generation sequencing, genome-wide association studies) have expanded the spectrum of both monogenic PD and variants that alter risk to develop PD. Examples of risk genes include the two lysosomal enzyme coding genes GBA and SMPD1, which are associated with a 5-fold and 9-fold increased risk of PD, respectively. It is hoped that further knowledge of the genetic makeup of PD will allow designing treatments that alter the course of the disease.

Keywords: Molecular mechanisms; Monogenic forms; Parkinson; Risk genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Parkinson Disease / genetics*
  • Risk Factors