Mehrdad A Estiar1,2, Konstantin Senkevich2,3, Eric Yu1,2, Parizad Varghaei2,4, Lynne Krohn1,2, Sara Bandres-Ciga5, Alastair J Noyce6,7, Guy A Rouleau1,2,3, Ziv Gan-Or1,2,3. 1. Department of Human Genetics, McGill University, Montréal, Québec, Canada. 2. The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montréal, Québec, Canada. 3. Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada. 4. Division of Experimental Medicine, Department of Medicine, McGill University, Montréal, Québec, Canada. 5. Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA. 6. Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom. 7. Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, United Kingdom.
Abstract
BACKGROUND: Epidemiological studies have reported an association between Parkinson's disease (PD) and restless legs syndrome. OBJECTIVES: We aimed to use genetic data to study whether these 2 disorders are causally linked or share genetic architecture. METHODS: We performed two-sample Mendelian randomization and linkage disequilibrium score regression using summary statistics from recent genome-wide meta-analyses of PD and restless legs syndrome. RESULTS: We found no evidence for a causal relationship between restless legs syndrome (as the exposure) and PD (as the outcome, inverse variance-weighted; b = -0.003, SE = 0.031, P = 0.916; F statistic = 217.5). Reverse Mendelian randomization also did not demonstrate any causal effect of PD on restless legs syndrome (inverse variance-weighted; b = -0.012, SE = 0.023, P = 0.592; F statistic = 191.7). Linkage disequilibrium score regression analysis demonstrated lack of genetic correlation between restless legs syndrome and PD (rg = -0.028, SE = 0.042, P = 0.507). CONCLUSIONS: There was no evidence for a causal relationship or genetic correlation between restless legs syndrome and PD. The associations observed in epidemiological studies could be attributed, in part, to confounding or nongenetic determinants.
BACKGROUND: Epidemiological studies have reported an association between Parkinson's disease (PD) and restless legs syndrome. OBJECTIVES: We aimed to use genetic data to study whether these 2 disorders are causally linked or share genetic architecture. METHODS: We performed two-sample Mendelian randomization and linkage disequilibrium score regression using summary statistics from recent genome-wide meta-analyses of PD and restless legs syndrome. RESULTS: We found no evidence for a causal relationship between restless legs syndrome (as the exposure) and PD (as the outcome, inverse variance-weighted; b = -0.003, SE = 0.031, P = 0.916; F statistic = 217.5). Reverse Mendelian randomization also did not demonstrate any causal effect of PD on restless legs syndrome (inverse variance-weighted; b = -0.012, SE = 0.023, P = 0.592; F statistic = 191.7). Linkage disequilibrium score regression analysis demonstrated lack of genetic correlation between restless legs syndrome and PD (rg = -0.028, SE = 0.042, P = 0.507). CONCLUSIONS: There was no evidence for a causal relationship or genetic correlation between restless legs syndrome and PD. The associations observed in epidemiological studies could be attributed, in part, to confounding or nongenetic determinants.
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