Noyce, A; (2021) Lack of Causal Effects or Genetic Correlation between Restless Legs Syndrome and Parkinson's Disease. Movement Disorders , 36 (8) pp. 1967-1972. 10.1002/mds.28640.

Text Noyce_Manuscript RLS-PD MR 05-04-2021 clean.pdf - Accepted Version Access restricted to UCL open access staff Download (212kB)

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. © 2021 International Parkinson and Movement Disorder Society

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