BACKGROUND The rise of direct-to-consumer genetic testing has enabled many to learn of their possible increased risk for rare diseases, some of which may be suitable for gene-targeted therapies. However, recruiting a large and representative population for rare diseases or genetically defined sub-populations of common diseases is slow, difficult, and expensive. OBJECTIVE To assess the feasibility of recruiting and retaining a cohort of individuals who carry a genetic mutation linked to Parkinson's disease (G2019S variant of LRRK2); to characterize this cohort relative to the characteristics of traditional, in-person studies; and to evaluate this model's ability to create an engaged study cohort interested in future clinical trials of gene-directed therapies. METHODS This single-site,3-year national longitudinal observational study will recruit between 250 to 350 LRRK2 carriers without Parkinson's disease and approximately 50 with the condition. Participants must have undergone genetic testing by the personal genetics company, 23andMe, Inc., have knowledge of their carrier status, and consent to be contacted for research studies. All participants undergo standardized assessments, including video-based cognitive and motor examination, and complete patient-reported outcomes on an annual basis. RESULTS 263 individuals living in 33 states have enrolled. The cohort has a mean (SD) age of 56.0 (15.9) years, 59% are female, and 76% are of Ashkenazi Jewish descent. 233 have completed the baseline visit: 47 with self-reported Parkinson's disease and 186 without. CONCLUSIONS This study establishes a promising model for developing a geographically dispersed and well-characterized cohort ready for participation in future clinical trials of gene-directed therapies.

中文翻译：

---

帕金森病遗传风险个体的虚拟队列研究：研究方案和设计。

背景直接面向消费者的基因检测的兴起使许多人了解到他们患罕见疾病的风险可能增加，其中一些可能适用于基因靶向治疗。然而，为罕见疾病或遗传定义的常见疾病亚群招募大量具有代表性的人群是缓慢、困难且昂贵的。目的 评估招募和保留一组携带与帕金森病相关基因突变（LRRK2 的 G2019S 变体）的个体的可行性；相对于传统的面对面研究的特征来表征该队列；并评估该模型创建对基因导向疗法的未来临床试验感兴趣的参与研究队列的能力。方法这个单站点，为期 3 年的国家纵向观察研究将招募 250 至 350 名没有帕金森病的 LRRK2 携带者和大约 50 名患有帕金森病的携带者。参与者必须经过个人遗传公司 23andMe, Inc. 的基因检测，了解其携带者身份，并同意被联系进行研究。所有参与者都接受标准化评估，包括基于视频的认知和运动检查，并每年完成患者报告的结果。结果 居住在 33 个州的 263 人已注册。该队列的平均 (SD) 年龄为 56.0 (15.9) 岁，59% 为女性，76% 为德系犹太人后裔。233 人完成了基线访视：47 人自我报告患有帕金森病，186 人没有。