Database of evidence-based ranked Parkinson Disease variants (P1.199)
Objective: To create a web database that can provide interpretation of the significance of single variant changes (SV) in Parkinson Disease (PD).
Background: Evaluation of genetic variants in PD can be difficult, as even rare or deleterious variants may not lead to disease. The introduction of next generation sequencing (NGS) has significantly increased the rate these variants are reported, changing the focus of research in PD from gene-based to SV. Thus, there is a need for a new kind of genetic database, capable of ranking and handling NGS data. The proposed work would fill this gap by creating a ranking scale for each variant based on current documentation and additional in-silico analyses and make recommendations about the strength of evidence for their significance to PD.
Methods: SV included will come from the literature and existing NGS databases. SV are ranked in each of three evidence levels: 1) “Genetic evidence” (e.g. population frequency, family segregation) and 2) “functional evidence” extracted from literature and data repositories and 3) in-silico analyses for all variants to determine potential functional effect of the variants (“in-silico evidence”) (e.g. PolyPhen2 for nonsynonymous, RegulomeDB and GWAVA for non-coding variants).
Results: Each variant is placed in one of six categories, based on the strength of evidence from the three evidence-levels, and this data will be available through a website. Summary data for each dataset and/or for each SV will be linked to the NGS laboratory or publication, to facilitate collaborative efforts.
Conclusions: The database will allow users to quickly evaluate variants and initiate collaborations. The summary data format avoids individual identifiers thus allowing rapid availability of NGS data to the PD research community. The database meets recommendations by NINDS PD2014.
Study was supported by a grant from the Department of Defense. Disclosure: Athena diagnostics, royalty CMT2A gene, received through Duke University., Dr. Wang has nothing to disclose. Dr. Beecham has nothing to disclose. Dr. Van Broeckhoven has nothing to disclose. Dr. Nuytemans has nothing to disclose.