Objective: Characterize the interactions between lifestyle, environmental, and genetic exposures on susceptibility to Parkinson’s disease (PD) and progression rates through a scalable remote web-based multimodal data collection platform.

Background: Causative factors in the development, phenotypic expression, and progression rates in PD are unclear. Known monogenic variants explain 10–15% of disease predisposition, leaving the majority of risk to lifestyle, environmental exposures, and other genetic drivers. Longitudinal studies are critical to determining PD risk and progression; however, these studies are often limited in scale, especially when collecting in vivo measurements, and are underpowered to detect gene-by-environment interactions. To address this, the 23andMe Research Institute launched the Parkinson’s Impact Project 2.0 (PIP 2.0)—a five-year multimodal prospective cohort of genotyped individuals.

Method: Consented research participants ≥40 years of age were enrolled and classified into three groups: 1) self-reported PD cases; 2) at-risk participants: carriers of high-risk variants (e.g., LRRK2 G2019S, GBA1 N409S), first-degree relative with PD, or self-reported prodromal features (hyposmia, REM sleep behavior disorder, autonomic dysfunction); 3) controls with no known risk or prodromal features. Data collection included annual self-report surveys covering symptoms of synuclein-mediated neurodegeneration, environmental and lifestyle factors, and medications (e.g., pressor agents, stool softeners, GLP-1 agonists). Participants could opt-in to sharing electronic medical records (EMRs) and wearable device data, and could participate in objective validated cognitive and sensory assessments, like the digit-symbol substitution task (DSST) and a speech-in-noise hearing test.

Results: A total of 56,116 participants have enrolled, including 3,072 PD cases (3% LRRK2 G2019S, 1% GBA1 N409S), 22,029 at-risk participants, and 31,015 controls. GLP-1 usage was reported by 2% of PD participants and 8% of at-risk/controls. In total, 3% of participants opted for EMR data sharing, 9% are actively sharing wearable data (e.g., daily steps), and 23% and 30% have taken the DSST and hearing test, respectively.

Conclusion: PIP 2.0 is an ongoing scalable online study that will provide rich, multimodal phenotyping needed at scale for informed risk and progression modeling of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-parkinsons-impact-project-a-multimodal-longitudinal-study-of-disease-development-and-progression-at-the-23andme-research-institute/