Genetic markers of Restless Legs Syndrome in Parkinson disease

Ziv Gan-Or, Roy N. Alcalay, Anat Bar-Shira, Claire S. Leblond, Ronald B. Postuma, Shay Ben-Shachar, Cheryl Waters, Amelie Johnson, Oren Levy, Anat Mirelman, Mali Gana-Weisz, Nicolas Dupré, Jacques Montplaisir, Nir Giladi, Stanley Fahn, Lan Xiong, Patrick A. Dion, Avi Orr-Urtreger, Guy A. Rouleau*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish
Pages (from-to)582-585
Number of pages4
JournalParkinsonism and Related Disorders
Issue number6
StatePublished - 1 Jun 2015


FundersFunder number
National Institutes of HealthUL1 TR000040
National Institute of Neurological Disorders and StrokeK02NS080915
Parkinson's Disease Foundation
Canadian Institutes of Health Research
Parkinson Society Canada


    • Genetics
    • Parkinson disease
    • Restless legs syndrome


    Dive into the research topics of 'Genetic markers of Restless Legs Syndrome in Parkinson disease'. Together they form a unique fingerprint.

    Cite this