Observational studies in Parkinson’s disease (PD) deeply characterize relatively small numbers of participants. The Molecular Integration in Neurological Diagnosis Initiative seeks to characterize molecular and clinical features of every PD patient at the University of Pennsylvania (UPenn). The objectives of this study are to determine the feasibility of genetic characterization in PD and assess clinical features by sex and GBA1/LRRK2 status on a clinic-wide scale. All PD patients with clinical visits at the UPenn PD Center between 9/2018 and 12/2022 were eligible. Blood or saliva were collected, and a clinical questionnaire administered. Genotyping at 14 GBA1 and 8 LRRK2 variants was performed. PD symptoms were compared by sex and gene groups. 2063 patients were approached and 1,689 (82%) were enrolled, with 374 (18%) declining to participate. 608 (36%) females were enrolled, 159 (9%) carried a GBA1 variant, and 44 (3%) carried a LRRK2 variant. Compared with males, females across gene groups more frequently reported dystonia (53% vs 46%, p = 0.01) and anxiety (64% vs 55%, p < 0.01), but less frequently reported cognitive impairment (10% vs 49%, p < 0.01) and vivid dreaming (53% vs 60%, p = 0.01). GBA1 variant carriers more frequently reported anxiety (67% vs 57%, p = 0.04) and depression (62% vs 46%, p < 0.01) than non-carriers; LRRK2 variant carriers did not differ from non-carriers. We report feasibility for near-clinic-wide enrollment and characterization of individuals with PD during clinical visits at a high-volume academic center. Clinical symptoms differ by sex and GBA1, but not LRRK2, status.

帕金森病 (PD) 的观察性研究深入描述了相对较少的参与者的特征。神经学诊断中的分子整合计划旨在描述宾夕法尼亚大学 (UPenn) 每位 PD 患者的分子和临床特征。本研究的目的是确定 PD 遗传特征的可行性，并在临床范围内按性别和GBA1/LRRK2状态评估临床特征。 2018 年 9 月至 2022 年 12 月期间在宾夕法尼亚大学 PD 中心进行临床就诊的所有 PD 患者均符合资格。收集血液或唾液，并进行临床问卷调查。对 14 个GBA1和 8 个LRRK2变体进行了基因分型。 PD 症状按性别和基因组进行比较。我们联系了 2063 名患者，并招募了 1,689 名患者 (82%)，其中 374 名患者 (18%) 拒绝参加。 608 名 (36%) 女性参与研究，其中 159 名 (9%) 携带GBA1变异，44 名 (3%) 携带LRRK2变异。与男性相比，不同基因组的女性更频繁地报告肌张力障碍（53% vs 46%，p  = 0.01）和焦虑（64% vs 55%，p  < 0.01），但较少报告认知障碍（10% vs 49%，p  < 0.01）和生动的梦（53% vs 60%，p  = 0.01）。GBA1变异携带者 比非携带者更频繁地报告焦虑（67% vs 57%，p  = 0.04）和抑郁（62% vs 46%，p < 0.01）； LRRK2变异携带者与非携带者没有差异。我们报告了在大容量学术中心进行临床就诊期间对帕金森病患者进行近诊所范围入组和特征描述的可行性。临床症状因性别和GBA1状态而异，但LRRK2状态不同。