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

Area of Science:

• Genomics
• Neuroscience
• Population Genetics

Background:

• The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to elucidate the genetic underpinnings of Alzheimer's disease and related dementias (ADRD).
• Integration of whole genome sequencing (WGS) with diverse genetic, phenotypic, and harmonized datasets is crucial for understanding ADRD genetic architecture.

Purpose of the Study:

• To detail the genetic architecture and quality of the Alzheimer's Disease Sequencing Project release 4 (R4) whole genome sequences.
• To identify and characterize genetic variants, including single nucleotide polymorphisms, insertions/deletions, and structural variants, across diverse populations.

Main Methods:

• Uniform processing of WGS data from 36,361 ADSP samples (35,014 unique participants, 45% non-European ancestry) across 17 cohorts in 14 countries.
• Harmonization of extensive phenotypic data from 15,927 participants across 10 domains.
• Creation of a linkage disequilibrium reference panel using unrelated Alzheimer's disease cases and controls.

Main Results:

• Identification of 435 million genetic variants, including single nucleotide polymorphisms, insertions/deletions, and structural variants.
• Availability of annotations and quality control data for all identified variants and samples.
• Provision of detailed phenotypes for a significant subset of participants.

Conclusions:

• The ADSP R4 dataset provides a comprehensive resource for studying the genetic basis of Alzheimer's disease and related dementias.
• Publicly accessible data through the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) and other platforms facilitates research.
• The findings underscore the importance of diverse genomic data in understanding complex diseases.