The Foundational data initiative for Parkinsons disease (FOUNDIN-PD): enabling efficient translation from genetic maps to mechanism
Elisângela BressaniD, Xylena ReediD, Vikas BansaliD, Elizabeth D. HutchinsiD, Melanie M. Cobb, Michelle G. WebbiD, Eric B. AlsopiD, Francis P. Grenn, Anastasia IllarionovaiD, Natalia SavytskaiD, Ivo Violich, Stefanie Bröer, Noémia FernandesiD, Ramiyapriya Sivakumar, Alexandra G. BeilinaiD, Kimberley J. BillingsleyiD, Joos BerghauseniD, Caroline B. PantazisiD, Vanessa PitziD, Dhairya Patel, Kensuke DaidaiD, Bessie Meechoovet, Rebecca A. Reiman, Amanda Courtright-LimiD, Amber Logemann, , Cornelis BlauwendraatiD
Abstract
The FOUNdational Data INitiative for Parkinsons Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources for Parkinsons disease (PD). FOUNDIN-PD generated a multi-layered molecular dataset in a cohort of induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons, a major affected cell type in PD. The lines were derived from the Parkinsons Progression Markers Initiative study including participants with PD carrying monogenic PD (SNCA) variants, variants with intermediate effects and variants identified by genome-wide association studies and unaffected individuals. We generated genetic, epigenetic, regulatory, transcriptomic, and longitudinal cellular imaging data from iPSC-derived DA neurons to understand molecular relationships between disease associated genetic variation and proximate molecular events. These data reveal that iPSC-derived DA neurons provide a valuable cellular context and foundational atlas for modelling PD genetic risk. We have integrated these data into a FOUNDIN-PD data browser (https://www.foundinpd.org) as a resource for understanding the molecular pathogenesis of PD.
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