NIAGADS: A data repository for Alzheimer's disease and related dementia genomics

Abstract

The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) is the National Institute on Aging-designated national data repository for human genetics research on Alzheimer's disease and related dementias (ADRD). NIAGADS maintains a high-quality data collection for ADRD genetic/genomic research and supports genetics data production and analysis, including whole genome and exome sequence data from the Alzheimer's Disease Sequencing Project and other genotype/phenotype data, encompassing 211,000 samples. NIAGADS shares these data with hundreds of research groups around the world via the Data Sharing Service, a Federal Information Security Modernization Act moderate compliant cloud-based platform that fully supports the National Institutes of Health Genomic Data Sharing Policy. NIAGADS Open Access consists of multiple knowledge bases with genome-wide association summary statistics and rich annotations on the biological significance of genetic variants and genes across the human genome. As a one-stop access portal for Alzheimer's disease (AD) genetics, NIAGADS stands as a keystone in promoting collaborations to advance the understanding and treatment of AD. HIGHLIGHTS: The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) is a data repository for the storage of genetics and genomics data. NIAGADS houses data for Alzheimer's disease, related dementias, and healthy aging. NIAGADS offers open and qualified access data and knowledgebases to explore open access data. The Alzheimer's Disease Sequencing Project dataset is the largest Alzheimer's disease and related dementias joint called whole genome sequencing dataset (≈ 58,000 whole genomes).

Keywords: Alzheimer's Disease Sequencing Project; Alzheimer's disease; Alzheimer's disease and related dementias; National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site; bioinformatics; data repository; dementia; genetics; genomics; open access; qualified access; sequencing.

FIGURE 1

A, NIAGADS and ADSP timeline. B, ADSP data growth by releases. AD, Alzheimer's disease; ADSP, Alzheimer's Disease Sequencing Project; AIML, Artificial Intelligence Machine Learning; dbGaP, database of Genotypes and Phenotypes; DSS, Data Sharing Service; GCAD, Genome Center for Alzheimer's Disease; NIA, National Institute on Aging; NIAGADS, National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site; NHGRI, National Human Genome Research Institute; NIH, National Institutes of Health; PHC, Phenotype Harmonization Consortium; WES, whole exome sequencing; WGS, whole genome sequencing.

FIGURE 2

Layout of the NIAGADS platforms. NIAGADS shares controlled‐access human genetics/genomics data and open‐access genomic knowledge through an integrated system of interoperable data access platforms. The dual approaches facilitate broad data sharing while ensuring compliance with ethical and privacy standards. ADVP, AD Variant Portal; API, application program interface; DARM, Data Access Request Management system; DSS, Data Sharing Service; FILER, Functional Genomics Repository; NIAGADS, National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site.

FIGURE 3

NIAGADS at a glance. A, NIAGADS by the numbers. B, A global map of cohorts contributing to the NIAGADS data collection. C, The NIAGADS data collection breakdown by data types. ADSP, Alzheimer's Disease Sequencing Project; GWAS, genome‐wide association study; NIAGADS, National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site; QTL, quantitative trait loci; WGS, whole genome sequencing.

FIGURE 4

Alzheimer's Disease Sequencing Project Release 4 whole genome sequence data by cohort‐reported population.

FIGURE 5

NIAGADS open access knowledge bases and API architecture. See Methods S1 in supporting information for technical details. AI, artificial intelligence; API, application program interface; NIAGADS, National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site; NLP, natural language processing.

FIGURE 6

Flow diagram of the ADSP data production process. A unified data flow allows NIAGADS to manage and move files during the process and track the progress of all data processing and sharing activities, while ensuring compliance with NIH GDS policy. A straightforward and centralized coordination process is easy to understand and facilitates communication with all contributors. Data are dispatched to designated domain experts by data types. ADSP, Alzheimer's Disease Sequencing Project; DSS, Data Sharing Service; GDS, genomic data sharing; NACC, National Alzheimer's Coordinating Center; NCRAD, National Centralized Repository for Alzheimer's Disease and Related Dementias; NIAGADS, National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site; NIH, National Institutes of Health; QC, quality control; USUHS GATC, Uniformed Services University of the Health Sciences American Genome Center.