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

BackgroundEpidemiological studies have reported association between Parkinsons disease (PD) and restless legs syndrome (RLS). ObjectivesWe aimed to use genetic data to study whether these two disorders are causally linked or share genetic architecture. MethodsWe performed two-sample Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC) using summary statistics from recent genome-wide meta-analyses of PD and RLS. ResultsWe found no evidence for a causal relationship between RLS (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 MR also did not demonstrate any causal effect of PD on RLS (inverse variance-weighted; b=-0.012, se=0.023, p=0.592, F-statistic=191.7). LDSC analysis demonstrated lack of genetic correlation between RLS and PD (rg=-0.028, se=0.042, p=0.507). ConclusionsThere was no evidence for a causal relationship or genetic correlation between RLS and PD. The associations observed in epidemiological studies could be, in part, attributed to confounding or non-genetic determinants.