Lack of Causal Effects or Genetic Correlation between Restless Legs Syndrome and Parkinson's Disease

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. (c) 2021 International Parkinson and Movement Disorder Society