Progress in unraveling the genetic etiology of Parkinson disease in a genomic era

Trends Genet. 2015 Mar;31(3):140-9. doi: 10.1016/j.tig.2015.01.004. Epub 2015 Feb 20.


Parkinson disease (PD) and Parkinson-plus syndromes are genetically heterogeneous neurological diseases. Initial studies into the genetic causes of PD relied on classical molecular genetic approaches in well-documented case families. More recently, these approaches have been combined with exome sequencing and together have identified 15 causal genes. Additionally, genome-wide association studies (GWASs) have discovered over 25 genetic risk factors. Elucidation of the genetic architecture of sporadic and familial parkinsonism, however, has lagged behind that of simple Mendelian conditions, suggesting the existence of features confounding genetic data interpretation. Here we discuss the successes and potential pitfalls of gene discovery in PD and related disorders in the post-genomic era. With an estimated 30% of trait variance currently unexplained, tackling current limitations will further expedite gene discovery and lead to increased application of these genetic insights in molecular diagnostics using gene panel and exome sequencing strategies.

Keywords: Parkinson disease; gene identification studies; limitations; massive parallel sequencing; molecular diagnostics.

Publication types

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

MeSH terms

  • Exome / genetics*
  • Genetic Predisposition to Disease
  • Genome, Human / genetics*
  • Genome-Wide Association Study
  • Genomics*
  • Humans
  • Mutation
  • Parkinson Disease / genetics*
  • Parkinson Disease / therapy
  • Risk Factors
  • Sequence Analysis, DNA