Mendelian Randomization Analysis Reveals No Causal Relationship Between Plasma α-Synuclein and Parkinson's Disease

So far, the studies exploring plasma alpha-synuclein as a biomarker of Parkinson's disease (PD) have provided contradictory results. Here, we first employed the Mendelian randomization (MR) approach to elucidate their potential causal relationship. Five genetic instrumental variables of plasma alpha-synuclein were acquired from two publicly available datasets. Three independent genome-wide association studies of PD were used as outcome cohorts (PD cohorts 1, 2, and 3). Two-sample MR analyses were conducted using inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and leave-one-out methods. Though the IVW approach demonstrated positive plasma alpha-synuclein effect on the PD risk in three outcome cohorts (OR = 1.134, 1.164, and 1.189, respectively), the P values were all larger than 0.05. The conclusions were robust under complementary sensitivity analyses. Our results did not support the causal relationship between plasma alpha-synuclein and PD.

Automated summary

The studies exploring plasma alpha-synuclein as a biomarker of Parkinson's disease have conflicting results. This study used the Mendelian randomization approach to investigate the causal relationship between plasma alpha-synuclein and PD. Despite observing a positive effect of plasma alpha-synuclein on PD risk, the results did not support a causal relationship. The findings were robust across sensitivity analyses.