The metabolic profile predating the onset of Parkinson’s disease (PD) remains unclear. We aim to investigate the metabolites associated with incident and prevalent PD and their predictive values in the UK Biobank participants with metabolomics and genetic data at the baseline. A panel of 249 metabolites was quantified using a nuclear magnetic resonance analytical platform. PD was ascertained by self-reported history, hospital admission records and death registers. Cox proportional hazard models and logistic regression models were used to investigate the associations between metabolites and incident and prevalent PD, respectively. Area under receiver operating characteristics curves (AUC) were used to estimate the predictive values of models for future PD. Among 109,790 participants without PD at the baseline, 639 (0.58%) individuals developed PD after one year from the baseline during a median follow-up period of 12.2 years. Sixty-eight metabolites were associated with incident PD at nominal significance (P < 0.05), spanning lipids, lipid constituent of lipoprotein subclasses and ratios of lipid constituents. After multiple testing corrections (P < 9\(\times\)10⁻⁴), polyunsaturated fatty acids (PUFA) and omega-6 fatty acids remained significantly associated with incident PD, and PUFA was shared by incident and prevalent PD. Additionally, 14 metabolites were exclusively associated with prevalent PD, including amino acids, fatty acids, several lipoprotein subclasses and ratios of lipids. Adding these metabolites to the conventional risk factors yielded a comparable predictive performance to the risk-factor-based model (AUC = 0.766 vs AUC = 0.768, P = 0.145). Our findings suggested metabolic profiles provided additional knowledge to understand different pathways related to PD before and after its onset.

帕金森病 (PD) 发病前的代谢特征仍不清楚。我们的目标是利用基线代谢组学和遗传数据，研究与事件和流行的帕金森病相关的代谢物及其在英国生物银行参与者中的预测价值。使用核磁共振分析平台对一组 249 种代谢物进行了定量。 PD是通过自我报告的病史、入院记录和死亡登记来确定的。 Cox 比例风险模型和逻辑回归模型分别用于研究代谢物与帕金森病事件和流行病之间的关联。受试者工作特征曲线下面积 (AUC) 用于估计未来 PD 模型的预测值。在 109,790 名在基线时没有 PD 的参与者中，639 名 (0.58%) 人在基线一年后在 12.2 年的中位随访期内出现 PD。 68 种代谢物与 PD 事件相关，具有名义显着性 ( P < 0.05)，涵盖脂质、脂蛋白亚类的脂质成分和脂质成分的比率。经过多次测试校正（ P < 9 \(\times\) 10 ^-4 ），多不饱和脂肪酸（PUFA）和omega-6脂肪酸仍然与PD事件显着相关，并且PUFA与PD事件和流行PD共享。此外，14 种代谢物与流行的 PD 完全相关，包括氨基酸、脂肪酸、几种脂蛋白亚类和脂质比率。将这些代谢物添加到传统风险因素中，产生了与基于风险因素的模型相当的预测性能（AUC = 0.766 vs AUC = 0.768， P = 0.145）。 我们的研究结果表明，代谢谱提供了额外的知识，以了解与帕金森病发病前后相关的不同途径。