1. The Foundational Data Initiative for Parkinson Disease: Enabling efficient translation from genetic maps to mechanism
- Author
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Bressan, Elisangela, Reed, Xylena, Bansal, Vikas, Hutchins, Elizabeth, Cobb, Melanie M, Webb, Michelle G, Alsop, Eric, Grenn, Francis P, Illarionova, Anastasia, Savytska, Natalia, Violich, Ivo, Broeer, Stefanie, Fernandes, Noémia, Sivakumar, Ramiyapriya, Beilina, Alexandra, Billingsley, Kimberley J, Berghausen, Joos, Pantazis, Caroline B, Pitz, Vanessa, Patel, Dhairya, Daida, Kensuke, Meechoovet, Bessie, Reiman, Rebecca, Courtright-Lim, Amanda, Logemann, Amber, Antone, Jerry, Barch, Mariya, Kitchen, Robert, Li, Yan, Dalgard, Clifton L, Center, The American Genome, Rizzu, Patrizia, Hernandez, Dena G, Hjelm, Brooke E, Nalls, Mike, Gibbs, J Raphael, Finkbeiner, Steven, Cookson, Mark R, Van Keuren-Jensen, Kendall, Craig, David W, Singleton, Andrew B, Heutink, Peter, and Blauwendraat, Cornelis
- Subjects
Biological Sciences ,Genetics ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Stem Cell Research - Induced Pluripotent Stem Cell ,Neurosciences ,Stem Cell Research ,Aging ,Parkinson's Disease ,Neurodegenerative ,Brain Disorders ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,American Genome Center ,Parkinson disease ,dopaminergic neurons ,genetic risk ,induced pluripotent stem cell ,omics single-cell RNA sequencing single-cell ATAC sequencing SNCA LRRK2 GBA1 - Abstract
The Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources for Parkinson 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 Parkinson's Progression Markers Initiative study, which included participants with PD carrying monogenic PD 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 modeling PD genetic risk. We have integrated these data into a FOUNDIN-PD data browser as a resource for understanding the molecular pathogenesis of PD.
- Published
- 2023