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Hence, it is necessary to establish the causal link between vitamin C levels and PD, and further develop effective therapies or prevention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We selected 11 newly identified plasma vitamin C genetic variants from a large-scale plasma vitamin C GWAS dataset (n\u2009=\u200952,018) 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\u2009=\u200928,568). 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u00a0years) with 1 SD genetically increased vitamin C levels using IVW (beta\u2009=\u2009\u2212 1.134, 95% CI: [\u2212 2.515, 0.248],<jats:italic>P<\/jats:italic>\u2009=\u20090.108). 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\u00a0years using weighted median (beta\u2009=\u2009\u2212 1.750, 95% CI: [\u2212 3.396, \u2212 0.105],<jats:italic>P<\/jats:italic>\u2009=\u20090.037) and MR-Egger (beta\u2009=\u2009\u2212 2.592, 95% CI: [\u2212 4.623, \u2212 0.560],<jats:italic>P<\/jats:italic>\u2009=\u20090.012).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12967-021-02892-5","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T11:03:15Z","timestamp":1621854195000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Effect of plasma vitamin C levels on Parkinson\u2019s disease and age at onset: a Mendelian randomization study"],"prefix":"10.1186","volume":"19","author":[{"given":"Haijie","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longcai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifa","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1126-2888","authenticated-orcid":false,"given":"Guiyou","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"2892_CR1","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1007\/s12035-014-8946-8","volume":"52","author":"G Liu","year":"2015","unstructured":"Liu G, Bao X, Jiang Y, Liao M, Jiang Q, Feng R, Zhang L, Ma G, Chen Z, Wang G, et al. 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All participants gave informed consent in all the corresponding original studies, as described in the Methods. Here, our study is based on the large-scale GWAS datasets, and not the individual-level data. Hence, ethical approval was not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"221"}}