Genome sequencing of Lewy Body Dementia and Frontotemporal Dementia: a public resource for the study of Alzheimer's disease and related dementias

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The Intramural Research Program is the ideal environment to undertake a project of this magnitude. This project places the Intramural Research Program at the forefront of dementia research and will greatly accelerate the pace of genetic discovery within the field. We performed genome sequencing of 3,000 LBD cases, 3,000 FTD cases and 2,500 neurologically normal control subjects using the Illumina X10 Sequencing platform. We analyzed the genome sequence data to identify genetic loci that alter the risk of developing disease and age at disease onset (i.e. genetic modifiers of phenotype). We have made the genome sequence data generated from this project publicly available on the dbGaP and AMP-PD web portals. These data act as the cornerstone of a new online resource that researchers can access, analyze, and combine with their own data to increase their power to detect new genetic loci. In this way, this unique database will be augmented over time and will greatly accelerate the pace of genetic discovery within the field. Our genome sequencing project is consistent with the strategic goals of the NIA. It aims to understand the dynamics of the aging process by unraveling the complex biology of dementia (Goal A). Unraveling the biology underlying dementia will improve the health, well-being and independence of adults as they age by improving our understanding of the aging brain, Alzheimer's disease, and other neurodegenerative diseases (Goal D). We also hope that learning the genetics underlying dementia will provide therapeutic targets for drug discovery and ultimately lead to the development of effective interventions (Goal C). The intent of this project was to establish a public resource that will accelerate high-quality research within the field, and that will grow over time (Goal G and H). The work on this project is ongoing and is being extended.