Population-specific frequencies for LRRK2 susceptibility variants in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium

Mov Disord. 2013 Oct;28(12):1740-4. doi: 10.1002/mds.25600. Epub 2013 Aug 2.

Abstract

Background: Variants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease.

Methods: The Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries.

Results: Herein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups.

Conclusions: Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies.

Keywords: LRRK2; Parkinson's disease; association study; genetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Frequency*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genetics, Population
  • Genotype
  • Haplotypes
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Molecular Epidemiology
  • Parkinson Disease / epidemiology*
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide
  • Protein Serine-Threonine Kinases / genetics*

Substances

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