Objective: To support the efforts of the Global Parkinson’s Genetics Program (GP2, http://gp2.org/) Monogenic Hub, by developing an easy-to-use online platform for case/family submission.

Background: GP2 is an international collaborative effort that aims to improve understanding of the role of genetics in Parkinson’s disease (PD), and to make this knowledge widely available and actionable [1]. The Monogenic Hub represents one of the two major arms of GP2. It aims to perform whole-genome sequencing (WGS) for 5-10,000 patients over a period of ≈5 years, in order to discover novel genetic causes of PD, and to better characterize genetic modifiers influencing disease manifestation and progression. A priority of GP2 is diversity in research and researchers, with involvement of underrepresented populations as a specific aim [1-4].

Method: A team of clinicians and researchers with expertise in PD genetics collaborated with professionals in web design and development. Key items include a registration site to submit information regarding institutional ethical clearance for international data and sample sharing; and an electronic case report form (eCRF) to securely submit pseudonymized data of patients/families in whom a monogenic cause of PD is suspected. To maximize participation, especially from under-resourced settings [1-4], clinical-demographic and available genetic pre-screening datasets are designated as “Minimal”, “Core” and “Extended” (Table 1); cases with at least basic “Minimal” data are eligible for participation. Of note, all submitted cases will also undergo comprehensive genotyping based on Illumina Global Diversity Array.

Results: The website for the Monogenic Hub, including the Monogenic Portal (https://monogenic.gp2.org), was launched on 8^thFebruary 2021. Feedback from users is continually utilized to further refine the accessibility/user-experience of the platform.

Conclusion: We established an online platform for case/family submission within the Monogenic Hub of GP2. The collection of rich patient/family data will facilitate prioritization of samples for WGS, and enable deeper analysis, e.g., of genetic, clinical-demographic and environmental factors influencing disease expression [5,6]. WGS for the first 500 PD patients is currently underway and, it is hoped, will be the beginning of many successful collaborations, both within and beyond GP2.

References: [1] The Global Parkinson’s Genetics Program. GP2: The Global Parkinson’s Genetics Program. Mov Disord. First published: 29 January 2021. https://doi.org/10.1002/mds.28494. [2] Lim SY, Tan AH, Ahmad-Annuar A, Klein C, Tan LCS, Rosales RL, Bhidayasiri R, Wu YR, Shang HF, Evans AH, Pal PK, Hattori N, Tan CT, Jeon B, Tan EK, Lang AE. Parkinson’s disease in the Western Pacific Region. Lancet Neurol. 2019 Sep;18(9):865-879. doi: 10.1016/S1474-4422(19)30195-4. Epub 2019 Jun 4. PMID: 31175000. [3] Ben-Joseph A, Marshall CR, Lees AJ, Noyce AJ. Ethnic Variation in the Manifestation of Parkinson’s Disease: A Narrative Review. J Parkinsons Dis. 2020;10(1):31-45. doi: 10.3233/JPD-191763. PMID: 31868680; PMCID: PMC7029316. [4] Lim SY, Lim KB, Hor JW, Tan AH. Brief Clinical Rating Scales Should Not Be Overlooked. Mov Disord. 2020 Oct;35(10):1884-1885. doi: 10.1002/mds.28274. PMID: 33068479. [5] Klein C, Hattori N, Marras C. MDSGene: Closing Data Gaps in Genotype-Phenotype Correlations of Monogenic Parkinson’s Disease. J Parkinsons Dis. 2018;8(s1):S25-S30. doi: 10.3233/JPD-181505. PMID: 30584170; PMCID: PMC6311364. [6] Iwaki H, Blauwendraat C, Makarious MB, Bandrés-Ciga S, Leonard HL, Gibbs JR, Hernandez DG, Scholz SW, Faghri F; International Parkinson’s Disease Genomics Consortium (IPDGC), Nalls MA, Singleton AB. Penetrance of Parkinson’s Disease in LRRK2 p.G2019S Carriers Is Modified by a Polygenic Risk Score. Mov Disord. 2020 May;35(5):774-780. doi: 10.1002/mds.27974. Epub 2020 Jan 20. PMID: 31958187.

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