NIAGADS Alzheimer’s GenomicsDB: A resource for exploring Alzheimer’s Disease genetic and genomic knowledge

Abstract

INTRODUCTIONThe NIAGADS Alzheimer’s Genomics Database is an interactive knowledgebase for AD genetics that provides access to GWAS summary statistics datasets deposited at NIAGADS, a national genetics data repository for AD and related dementia (ADRD).METHODSThe website makes available >70 genome-wide summary statistics datasets from GWAS and genome sequencing analysis for AD/ADRD. Variants identified from these datasets are mapped to up-to-date variant and gene annotations from a variety of resources and linked to functional genomics data.The database is powered by a big-data optimized relational database and ontologies to consistently annotate study designs and phenotypes, facilitating data harmonization and efficient real-time data analysis and variant or gene report generation.RESULTSDetailed variant reports provide tabular and interactive graphical summaries of known ADRD associations, as well as highlight variants flagged by the Alzheimer’s Disease Sequencing Project (ADSP). Gene reports provide summaries of co-located ADRD risk-associated variants and have been expanded to include meta-analysis results from aggregate association tests performed by the ADSP allowing us to flag genes with genetic-evidence for AD.DISCUSSIONThe GenomicsDB makes available >100 million variant annotations, including ~30 million (5 million novel) variants identified as AD-relevant by ADSP, for browsing and real-time mining via the website or programmatically through a REST API. With a newly redesigned, efficient, search interface and comprehensive record pages linking summary statistics to variant and gene annotations, this resource makes these data both accessible and interpretable, establishing itself as valuable tool for AD research.

Alzheimer’s Disease variant portal (ADVP): a catalog of genetic findings for Alzheimer’s Disease

“…Lastly, the document is parsed by customized scripts to normalize, validate, annotate, and store the publication, variant, and association data in the relational database [33]. Collected AD variants and association records are further linked (using positional and variant and gene identifier information) with the NIAGADS Alzheimer’s Genomics Database [24] which provides the comprehensive annotation and functional genomic information. Supplementary Note 2 provides details on ADVP architecture and implementation.…”

“…Each genetic variant in ADVP is described using dbSNP rsID, genomic coordinates (chromosome:basepair), reference and alternative alleles. Both the information reported in the publication (if available) and those derived from the reference databases such as dbSNP [25] and NIAGADS Alzheimer’s Genomics database [24], are included in the variant description. Genomic location in ADVP is currently stored using GRCh37/hg19 reference genome build as the majority of GWAS publications conducted analyses using GRCh37/hg19.…”

“…All variants and association in ADVP were systematically annotated with genomic context (closest upstream/downstream genes), genomic element (promoter, UTR, intron, exon, intergenic, repeat), functional impact (variant most severe consequence), and cross-referenced to NIAGADS Alzheimer’s Genomics database [24].…”

“…We cross-checked recorded positional information (chromosome:basepair), rsID, and allele information against reference databases including, dbSNP [25], NIAGADS Alzheimer’s Genomics database [24], 1000 Genome data [31] to ensure variant information is correct.…”

“…All AD associations in ADVP are annotated with genomic and functional information. Comprehensive biological annotations are available via integration with the NIAGADS Alzheimer’s Disease Genomics database [24]. ADVP will serve as an invaluable resource for the research community to explore and decipher the genetic architecture of AD and other neurodegenerative diseases.…”