Genetic markers of Restless Legs Syndrome in Parkinson disease

Parkinsonism Relat Disord. 2015 Jun;21(6):582-5. doi: 10.1016/j.parkreldis.2015.03.010. Epub 2015 Mar 17.


Introduction: Several studies proposed that Restless Legs Syndrome (RLS) and Parkinson disease (PD) may be clinically and/or etiologically related. To examine this hypothesis, we aimed to determine whether the known RLS genetic markers may be associated with PD risk, as well as with PD subtype.

Methods: Two case-control cohorts from Tel-Aviv and New-York, including 1133 PD patients and 867 controls were genotyped for four RLS-related SNPs in the genes MEIS1, BTBD9, PTPRD and MAP2K5/SKOR1. The association between genotype, PD risk and phenotype was tested using multivariate regression models.

Results: None of the tested SNPs was significantly associated with PD risk, neither in any individual cohort nor in the combined analysis after correction for multiple comparisons. The MAP2K5/SKOR1 marker rs12593813 was associated with higher frequency of tremor in the Tel-Aviv cohort (61.0% vs. 46.5%, p = 0.001, dominant model). However, the risk allele for tremor in this gene has been associated with reduced RLS risk. Moreover, this association did not replicate in Tremor-dominant PD patients from New-York.

Conclusion: RLS genetic risk markers are not associated with increased PD risk or subtype in the current study. Together with previous genetic, neuropathological and epidemiologic studies, our results further strengthen the notion that RLS and PD are likely to be distinct entities.

Keywords: Genetics; Parkinson disease; Restless Legs Syndrome.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Genetic Markers / genetics*
  • Genetic Predisposition to Disease
  • Homeodomain Proteins / genetics
  • Humans
  • MAP Kinase Kinase 5 / genetics
  • Male
  • Middle Aged
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins / genetics
  • Nerve Tissue Proteins
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics
  • Restless Legs Syndrome / genetics*
  • Risk Factors
  • Transcription Factors / genetics


  • BTBD9 protein, human
  • Genetic Markers
  • Homeodomain Proteins
  • MEIS1 protein, human
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Transcription Factors
  • MAP Kinase Kinase 5
  • MAP2K5 protein, human
  • PTPRD protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2