There is considerable uncertainty regarding the associations between various risk factors and Parkinson’s Disease (PD). This study systematically screened and validated a wide range of potential PD risk factors from 502,364 participants in the UK Biobank. Baseline data for 1851 factors across 11 categories were analyzed through a phenome-wide association study (PheWAS). Polygenic risk scores (PRS) for PD were used to diagnose Parkinson’s Disease and identify factors associated with PD diagnosis through PheWAS. Two-sample Mendelian randomization (MR) analysis was employed to assess causal relationships. PheWAS results revealed 267 risk factors significantly associated with PD-PRS among the 1851 factors, and of these, 27 factors showed causal evidence from MR analysis. Compelling evidence suggests that fluid intelligence score, age at first sexual intercourse, cereal intake, dried fruit intake, and average total household income before tax have emerged as newly identified risk factors for PD. Conversely, maternal smoking around birth, playing computer games, salt added to food, and time spent watching television have been identified as novel protective factors against PD. The integration of phenotypic and genomic data may help to identify risk factors and prevention targets for PD.

各种危险因素与帕金森病 (PD) 之间的关联存在相当大的不确定性。这项研究从英国生物银行的 502,364 名参与者中系统地筛选和验证了各种潜在的 PD 风险因素。通过全表型关联研究 (PheWAS) 分析了 11 个类别的 1851 个因素的基线数据。 PD 多基因风险评分 (PRS) 用于诊断帕金森病，并通过 PheWAS 识别与 PD 诊断相关的因素。采用两个样本孟德尔随机化 (MR) 分析来评估因果关系。 PheWAS 结果显示，1851 个因素中有 267 个与 PD-PRS 显着相关，其中 27 个因素通过 MR 分析显示出因果证据。令人信服的证据表明，流体智力评分、首次性交年龄、谷物摄入量、干果摄入量和税前平均家庭总收入已成为新确定的 PD 风险因素。相反，母亲在出生前后吸烟、玩电脑游戏、食物中添加盐以及花时间看电视已被认为是预防帕金森病的新保护因素。表型和基因组数据的整合可能有助于确定帕金森病的危险因素和预防目标。