机构:[1]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.神经科系统神经内科首都医科大学宣武医院[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.首都医科大学宣武医院低氧适应转化医学北京市重点实验室[9]National Engineering Laboratory of Internet Medical Diagnosis and Treatment TechnologyXuanwu Hospital, Capital Medical University, Beijing 100053, China.首都医科大学宣武医院北京市神经药物工程技术研究中心
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.
基金:
This work was supported by funding from the National Natural Science
Foundation of China (Grant No. 82071212 and 81901181), the Mathematical
Tianyuan Fund of the National Natural Science Foundation of China
(Grant No. 12026414), and Beijing Ten Thousand Talents Project (Grant No.
2020A15). This work was also partially supported by funding from the Science
and Technology Beijing One Hundred Leading Talent Training Project
(Z141107001514006), the Beijing Municipal Administration of Hospitals’ Mission
Plan (SML20150802), the Funds of Academic Promotion Programme of
Shandong First Medical University & Shandong Academy of Medical Sciences
(No. 2019QL016, No. 2019PT007).
第一作者机构:[1]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
通讯作者:
推荐引用方式(GB/T 7714):
Haijie Liu,Yan Zhang,Haihua Zhang,et al.Effect of plasma vitamin C levels on Parkinson's disease and age at onset: a Mendelian randomization study.[J].JOURNAL OF TRANSLATIONAL MEDICINE.2021,19(1):221.doi:10.1186/s12967-021-02892-5.
APA:
Haijie Liu,Yan Zhang,Haihua Zhang,Longcai Wang,Tao Wang...&Guiyou Liu.(2021).Effect of plasma vitamin C levels on Parkinson's disease and age at onset: a Mendelian randomization study..JOURNAL OF TRANSLATIONAL MEDICINE,19,(1)
MLA:
Haijie Liu,et al."Effect of plasma vitamin C levels on Parkinson's disease and age at onset: a Mendelian randomization study.".JOURNAL OF TRANSLATIONAL MEDICINE 19..1(2021):221