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

Journal of Translational Medicine

Tao Wang¹  Haihua Zhang²  Guiyou Liu³  Longcai Wang⁴  Liyong Wu⁵  Haijie Liu⁵  Yan Zhang⁶  Zhifa Han⁷ 

[1] Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China;Chinese Institute for Brain Research, Beijing, China;Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, 100069, Beijing, China;Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, 100069, Beijing, China;Chinese Institute for Brain Research, Beijing, China;Beijing Key Laboratory of Hypoxia Translational Medicine, Xuanwu Hospital, Capital Medical University, 100053, Beijing, China;National Engineering Laboratory of Internet Medical Diagnosis and Treatment TechnologyXuanwu Hospital, Capital Medical University, 100053, Beijing, China;Department of Anesthesiology, The Affiliated Hospital of Weifang Medical University, 261053, Weifang, China;Department of Neurology, Xuanwu Hospital, Capital Medical University, 100053, Beijing, China;Department of Pathology, The Affiliated Hospital of Weifang Medical University, 261053, Weifang, China;School of Medicine, School of Pharmaceutical Sciences, THU-PKU Center for Life Sciences, Tsinghua University, Beijing, China;

关键词: Parkinson’s disease;    Vitamin C;    Genome-wide association study;    Mendelian randomization;    Inverse-variance weighted;   

DOI  :  10.1186/s12967-021-02892-5

来源: Springer

【 摘 要 】

BackgroundUntil 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.MethodsWe 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.ResultsWe 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).ConclusionsWe 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.

【 授权许可】

CC BY