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Effect of plasma vitamin C levels on Parkinson's disease and age at onset: a Mendelian randomization study.

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机构: [1]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. [2]Department of Pathology, The Affiliated Hospital of Weifang Medical University, Weifang 261053, China. [3]Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology,Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100069, China. [4]Department of Anesthesiology, The Affiliated Hospital of Weifang Medical University, Weifang 261053, China. [5]Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. [6]Chinese Institute for Brain Research, Beijing, China. [7]School of Medicine, School of Pharmaceutical Sciences, THU‑PKU Center for Life Sciences, Tsinghua University, Beijing, China. [8]Beijing Key Laboratory of Hypoxia Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. [9]National Engineering Laboratory of Internet Medical Diagnosis and Treatment TechnologyXuanwu Hospital, Capital Medical University, Beijing 100053, China.
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关键词: Parkinson’s disease Vitamin C Genome-wide association study Mendelian randomization Inversevariance weighted

摘要:
Until now, epidemiological evidence regarding the association between vitamin C intake (both diet and supplements) and Parkinson's disease (PD) remains inconsistent. Hence, it is necessary to establish the causal link between vitamin C levels and PD, and further develop effective therapies or prevention. We selected 11 newly identified plasma vitamin C genetic variants from a large-scale plasma vitamin C GWAS dataset (n = 52,018) as the effective instrumental variables, and extracted their corresponding GWAS summary statistics from PD (33,674 PD cases and 449,056 controls) and PD age at onset (AAO) (n = 28,568). We then performed a Mendelian randomization (MR) study to evaluate the causal association of plasma vitamin C levels with PD and PD AAO using inverse-variance weighted (IVW), the weighted median, MR-Egger, and MR-PRESSO test. We did not observe any significant association between genetically increased vitamin C levels and PD. Interestingly, we found a reduced trend of PD AAO (1.134 years) with 1 SD genetically increased vitamin C levels using IVW (beta = - 1.134, 95% CI: [- 2.515, 0.248], P = 0.108). Importantly, this trend was further successfully verified using both weighted median and MR-Egger. Each 1 SD genetically increased vitamin C levels could reduce PD AAO 1.75 and 2.592 years using weighted median (beta = - 1.750, 95% CI: [- 3.396, - 0.105], P = 0.037) and MR-Egger (beta = - 2.592, 95% CI: [- 4.623, - 0.560], P = 0.012). We demonstrated the causal association between genetically increased plasma vitamin C levels and reduced PD AAO in people of European descent. Randomized controlled trials are required to clarify whether diet intake or supplement, or both could reduce the AAO of PD.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 3 区 医学:研究与实验
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验
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出版当年[2019]版:
Q2 MEDICINE, RESEARCH & EXPERIMENTAL
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Q1 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者机构: [1]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
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