The role of the RFA-mandated Biostatistics and Data Analysis Core (Core C) in the Coordinating Center for Genetics and Genomics of Alzheimer's Disease (CGAD) is to design and implement all aspects of the analysis of Alzheimer's Disease Sequence Project (ADSP) and non-ADSP data (Combined Discovery, Replication and Extended Replication Phases). This analysis design will occur in collaboration with all ADSP/RFA-AG-16002 UO1 and other AD genetics investigators with Core C leading this interaction. To this end, Core C personnel will work with Core A to establish mechanisms for CGAD and other ADSP investigators to work together. The mission of the Core is to design analyses that make use of all available Alzheimer disease (AD)-relevant genetics data including whole genome sequence (WGS) and whole exome sequence (WES) from the ADSP Discovery Phase, targeted genome sequence (TGS) from the Replication Phases, non-ADSP sequence data, and genome-wide single nucleotide variant (SNV) data from large cohorts. Core C will design harmonization protocols for genetic data. Core B will execute these protocols to prepare analysis-ready files for Core C analysis. Special consideration will be given to family-based analyses because the multiplex kindreds being used by the ADSP and non-ADSP groups for sequencing have additional subjects that are not being sequenced but with genome-wide SNV data available. Special consideration will also be given to analyzing African American and Caribbean Hispanic data. Core C tasks will be: 1) re-evaluate the Discovery Phase analyses for additional findings that may be considered in the Replication Phase; 2) design and conduct Replication Phase analyses; 3) design and conduct comprehensive analyses of the aggregate Discovery and Replication Phase data; 4) design and conduct analyses to incorporate genetic data generated outside the ADSP for subjects and families used in the ADSP discovery and Replication Phases; 5) design and conduct the Extended Replication Phase analyses to incorporate genetic data from subjects and cohorts not directly involved in the ADSP project; 6) design post analyses; 7) develop novel analyses approaches.
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