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

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Abstract

So far, the studies exploring plasma α-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 α-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 α-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 α-synuclein and PD.

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Data Availability

The relevant GWAS summary statistics used in this work were publicly available, and the source was described appropriately in the main text.

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Acknowledgements

We sincerely thank the researchers who performed the relevant GWAS and made the summary statistics publicly available. Their contributions were cited appropriately in the main text.

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Author notes

  1. Qi Zhang and Zenan Lin contributed equally to this work and should be considered as joint first authors.

Authors and Affiliations

  1. The Department of Neurology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, Jiangsu, China

    Qi Zhang

  2. Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China

    Zenan Lin & Junhong Jiang

  3. The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, The State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China

    Yan He

  4. Children’s Hospital of Fudan University, No.399 Wanyuan Road, Shanghai, 201102, China

    Di Hu

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  1. Qi Zhang
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Contributions

Junhong Jiang: conceptualization, methodology, and writing; Qi Zhang and Zenan Lin: methodology, investigation, analysis of data, and writing; Yan He: analysis of data; Di Hu: supervision, conceptualization, and writing. The authors approved the final version of the submitted manuscript.

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Correspondence to Junhong Jiang or Di Hu.

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Zhang, Q., Lin, Z., He, Y. et al. Mendelian Randomization Analysis Reveals No Causal Relationship Between Plasma α-Synuclein and Parkinson’s Disease. Mol Neurobiol 60, 2268–2276 (2023). https://doi.org/10.1007/s12035-023-03206-0

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