Assessing the association between white matter lesions and Parkinson's disease

Abstract

Background: The association between white matter (WM) lesions and Parkinson's disease (PD) was not fully established. We therefore applied Mendelian randomization (MR) analyses to identify the causal effect between white matter lesions and PD.

Methods: We performed a bidirectional two-sample Mendelian randomization (MR) study to investigate the association between three WM phenotypes-white matter hyperintensities (WMH, N = 18,381), fractional anisotropy (FA, N = 17,673), and mean diffusivity (MD, N = 17,467)-with PD (N = 482,730) using summary statistics from genome-wide association studies (GWAS). The inverse variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO methods were used to evaluate the causal estimate.

Results: Significant evidence was suggested that higher MD was associated with a higher PD risk (OR = 1.049, 95% CI = 1.018-1.081, p = 0.022) when the outlier was removed using MR-PRESSO method. Moreover, genetically predicted PD was associated with a lower WMH load (IVW β = - 0.047, 95% CI = - 0.085 to - 0.009, p = 0.016) and a higher FA (β = 0.185, 95% CI = 0.021-0.349, p = 0.027). No evidence of pleiotropy was found using MR-Egger intercept.

Conclusion: Our findings provided genetic support that white matter microstructural integrity lesions might increase the risk of PD. However, genetically predicted PD was potentially associated with a lower load of white matter lesions.

Keywords: Causality; Mendelian randomization; Parkinson’s disease; White matter hyperintensity; White matter lesions.