Genetic architecture of Parkinson’s disease subtypes – Review of the literature

Jarosław Dulski, Ryan J. Uitti, Owen A. Ross, Zbigniew K. Wszolek

Research output: Contribution to journalReview articlepeer-review

Abstract

The heterogeneity of Parkinson’s disease (PD) has been recognized since its description by James Parkinson over 200 years ago. The complexity of motor and non-motor PD manifestations has led to many attempts of PD subtyping with different prognostic outcomes; however, the pathophysiological foundations of PD heterogeneity remain elusive. Genetic contributions to PD may be informative in understanding the underpinnings of PD subtypes. As such, recognizing genotype-phenotype associations may be crucial for successful gene therapy. We review the state of knowledge on the genetic architecture underlying PD subtypes, discussing the monogenic forms, as well as oligo- and polygenic risk factors associated with various PD subtypes. Based on our review, we argue for the unification of PD subtyping classifications, the dichotomy of studies on genetic factors and genetic modifiers of PD, and replication of results from previous studies.

Original languageEnglish (US)
Article number1023574
JournalFrontiers in Aging Neuroscience
Volume14
DOIs
StatePublished - Oct 20 2022

Keywords

  • PD
  • genome-wide association study (GWAS)
  • genotype
  • heterogeneity
  • monogenic
  • oligogenic and polygenic inheritance
  • phenotype

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience

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