Baseline genetic associations in the Parkinson's Progression Markers Initiative (PPMI)

Mov Disord. 2016 Jan;31(1):79-85. doi: 10.1002/mds.26374. Epub 2015 Aug 13.

Abstract

Background: The Parkinson's Progression Marker Initiative is an international multicenter study whose main goal is investigating markers for Parkinson's disease (PD) progression as part of a path to a treatment for the disease. This manuscript describes the baseline genetic architecture of this study, providing not only a catalog of disease-linked variants and mutations, but also quantitative measures with which to adjust for population structure.

Methods: Three hundred eighty-three newly diagnosed typical PD cases, 65 atypical PD and 178 healthy controls, from the Parkinson's Progression Marker Initiative study have been genotyped on the NeuroX or Immunochip arrays. These data are freely available to all researchers interested in pursuing PD research within the Parkinson's Progression Marker Initiative.

Results: The Parkinson's Progression Marker Initiative represents a study population with low genetic heterogeneity. We recapitulate known PD associations from large-scale genome-wide association studies and refine genetic risk score models for PD predictability (area under the curve, ∼0.74). We show the presence of six LRRK2 p.G2019S and nine GBA p.N370S mutation carriers.

Conclusions: The Parkinson's Progression Marker Initiative study and its genetic data are useful in studies of PD biomarkers. The genetic architecture described here will be useful in the analysis of myriad biological and clinical traits within this study.

Keywords: GWAS; Parkinson's disease; genetic risk score; genetics.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Area Under Curve
  • Disease Progression*
  • Dopamine / deficiency
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Glucosylceramidase / genetics*
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Male
  • Meta-Analysis as Topic
  • Microchip Analytical Procedures
  • Middle Aged
  • Mutation / genetics*
  • Parkinson Disease / genetics*
  • Parkinson Disease / physiopathology
  • Principal Component Analysis
  • Protein Serine-Threonine Kinases / genetics*

Substances

  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases
  • Glucosylceramidase
  • Dopamine