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Assessing the association between white matter lesions and Parkinson's disease
Yahui Zhu1,2, Rongrong Du2,3, Zhengqing He1,2
1Medical School of Chinese PLA, Beijing, China.
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.
Insights
White matter lesions, particularly higher mean diffusivity, may increase Parkinson's disease (PD) risk. Conversely, genetically predicted PD might be linked to reduced white matter lesions and increased fractional anisotropy.
Area of Science:
- Neuroscience
- Genetics
- Epidemiology
Background:
- The relationship between white matter (WM) lesions and Parkinson's disease (PD) requires further clarification.
- Mendelian randomization (MR) is a robust method for investigating potential causal links between genetic variants and disease outcomes.
Purpose of the Study:
- To investigate the potential causal effects of white matter hyperintensities (WMH), fractional anisotropy (FA), and mean diffusivity (MD) on Parkinson's disease (PD) risk.
- To explore the potential causal effect of genetically predicted PD on WM phenotypes using a bidirectional MR approach.
Main Methods:
- A bidirectional two-sample Mendelian randomization (MR) study was conducted using genome-wide association study (GWAS) summary statistics.
- Three WM phenotypes (WMH, FA, MD) and PD were analyzed for associations.
- Standard MR methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were employed to assess causality and pleiotropy.
Main Results:
- Higher mean diffusivity (MD) was significantly associated with an increased risk of Parkinson's disease (PD).
- Genetically predicted PD showed an association with a lower white matter hyperintensity (WMH) load.
- Genetically predicted PD was also associated with higher fractional anisotropy (FA), indicating improved white matter integrity.
Conclusions:
- The findings provide genetic evidence suggesting that white matter microstructural integrity lesions may elevate the risk of developing Parkinson's disease.
- Conversely, genetically predicted Parkinson's disease may be associated with a reduced burden of white matter lesions.
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