In order to systematically describe the Parkinson’s disease phenome, we performed a series of 832 cross-sectional case-control analyses in a large database. Responses to 832 online survey-based phenotypes including diseases, medications, and environmental exposures were analyzed in 23andMe research participants. For each phenotype, survey respondents were used to construct a cohort of Parkinson’s disease cases and age-matched and sex-matched controls, and an association test was performed using logistic regression. Cohorts included a median of 3899 Parkinson’s disease cases and 49,808 controls, all of European ancestry. Highly correlated phenotypes were removed and the novelty of each significant association was systematically assessed (assigned to one of four categories: known, likely, unclear, or novel). Parkinson’s disease diagnosis was associated with 122 phenotypes. We replicated 27 known associations and found 23 associations with a strong a priori link to a known association. We discovered 42 associations that have not previously been reported. Migraine, obsessive-compulsive disorder, and seasonal allergies were associated with Parkinson’s disease and tend to occur decades before the typical age of diagnosis for Parkinson’s disease. The phenotypes that currently comprise the Parkinson’s disease phenome have mostly been explored in relatively small purpose-built studies. Using a single large dataset, we have successfully reproduced many of these established associations and have extended the Parkinson’s disease phenome by discovering novel associations. Our work paves the way for studies of these associated phenotypes that explore shared molecular mechanisms with Parkinson’s disease, infer causal relationships, and improve our ability to identify individuals at high-risk of Parkinson’s disease.

为了系统地描述帕金森病表型，我们在一个大型数据库中进行了一系列 832 个横断面病例对照分析。23andMe 研究参与者对 832 项基于在线调查的表型（包括疾病、药物和环境暴露）的反应进行了分析。对于每种表型，调查受访者被用来构建一组帕金森病病例以及年龄匹配和性别匹配的对照，并使用逻辑回归进行关联测试。队列中包括 3899 名帕金森病病例和 49,808 名对照者，全部都是欧洲血统。去除高度相关的表型，并系统地评估每个显着关联的新颖性（分配到四个类别之一：已知、可能、不清楚或新颖）。帕金森病的诊断与 122 种表型相关。我们复制了 27 个已知关联，发现 23 个关联与已知关联有很强的先验联系。我们发现了 42 个以前从未报道过的关联。偏头痛、强迫症和季节性过敏与帕金森病有关，并且往往比帕金森病的典型诊断年龄早几十年发生。目前构成帕金森病表型的表型大多是在相对较小的专门研究中进行探索的。使用单个大型数据集，我们成功地重现了许多已建立的关联，并通过发现新的关联扩展了帕金森病的表型。我们的工作为研究这些相关表型铺平了道路，探索与帕金森病的共同分子机制，推断因果关系，并提高我们识别帕金森病高风险个体的能力。