The Alzheimer Disease Sequencing Project: Enabling Discovery Through Diversity

Abstract

AbstractBackgroundIn 2011, the U.S. congress passed the National Alzheimer’s Project Act to address the rapidly growing problem of Alzheimer disease and related disorders (ADRD). In response, the National Institute on Aging (NIA) initiated the Alzheimer’s Disease Sequencing Project (ADSP), a large‐scale effort to leverage genetics and genomics technology and expertise to unravel the underlying fundamental understanding of ADRD and accelerate the development of effective treatments for ADRD.MethodThe ADSP initially assembled existing datasets and now has invested heavily in developing new datasets (through the Follow‐Up Study (FUS) and Family‐Based Study (FBS) efforts) representing global diversity, now spanning nearly every continent. Necessary and critical infrastructure is in place, including the Genome Center for Alzheimer Disease (GCAD; DNA sequence processing), the NIA Genetics of Alzheimer Disease Data Storage Site (NIAGADS; data repository and access), and the National Centralized Repository for Alzheimer disease (NCRAD: sample repository). Data generation is performed through centralized laboratories for both whole genome sequencing (WGS) and plasma biomarkers. The resulting data are analyzed through multiple complementary consortia including those for data harmonization, genetic analysis, functional genomics, and computational analysis. This collaborative global initiative is coordinated through an oversight committee (the Executive Committee‐Cross Consortium Collaboration and Coordination; EC‐4C) with representation from all these important groups.ResultsData is released to the research community on a regular basis with the most recent release containing ∼37,000 WGS.ConclusionFuture releases will contain more detailed and harmonized clinical information, plasma biomarkers, WGS, and multi‐omics data, with the goal of having >100,000 samples with strong representation of global diversity.