Alzheimer's Disease Sequencing Project release 4 whole genome sequencing dataset

INTRODUCTION: The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to understand the genetic architecture of Alzheimer's disease and related dementias (ADRD) by integrating whole genome sequencing (WGS) with other genetic, phenotypic, and harmonized datasets from diverse populations. METHODS: The Genome Center for Alzheimer's Disease (GCAD) uniformly processed WGS from 36,361 ADSP samples, including 35,014 genetically unique participants of which 45% are from non-European ancestry, across 17 cohorts in 14 countries in this fourth release (R4). RESULTS: This sequencing effort identified 387 million bi-allelic variants, 42 million short insertions/deletions, and 6.8 million structural variants. Annotations and quality control data are available for all variants and samples. Additionally, detailed phenotypes from 15,927 participants across 10 domains are also provided. A linkage disequilibrium panel was created using unrelated AD cases and controls. DISCUSSION: Researchers can access and analyze the genetic data via the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) Data Sharing Service, the VariXam, or NIAGADS GenomicsDB. Highlights: We detailed the genetic architecture and quality of the Alzheimer's Disease Sequencing Project release 4 whole genome sequences. We identified 435 million single nucleotide polymorphisms, insertions and deletions, and structural variants from diverse genomes. We harmonized extensive phenotypes, linkage disequilibrium reference panel on subset of samples. Data is publicly available at NIAGADS Data Storage Site, variants and annotations are browsable on two different websites.