# The Alzheimer Disease Sequence Analysis Collaborative

> **NIH NIH U01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $2,886,114

## Abstract

The Alzheimer's Disease Sequencing Project (ADSP) is a national sequencing initiative focused on identifying
genetic variants that either protect from or increase the risk for late onset Alzheimer Disease (LOAD), with the
goal of accelerating development of effective therapeutics. The ADSP Discovery phase includes whole exome
sequencing (WES) of 10,571 unrelated non-Hispanic White (NHW) cases (N=5,606) and controls (N=4,965),
and whole genome sequencing (WGS) of 578 NHW and Hispanic (HI) familial samples. The Discovery Extension
Phase of the project added WGS on 434 new familial samples and 3,343 NHW, AA, and HI cases and controls
(collectively the ADSP-DEP). Preliminary analyses of these data confirm known LOAD genes and point toward
several new LOAD-related genes and their functional relationships to APP processing, neuroinflammation,
endocytosis, and cholesterol metabolism. The current Follow-Up Study phase (ADSP-FUS) will generate
>15,000 additional WGS focused on samples that `encompass the richest possible ethnic diversity', which will
include primarily HI and African-American (AA) datasets. This combination of diverse datasets derived from
case-control, cohort, and family study designs requires an intensive and comprehensive analytical effort to
uncover the wealth of information sequestered in the WGS. We (the Collaboration on Alzheimer Disease
REsearch [CADRE]) hypothesize that protective and risk genomic variants will provide potential therapeutic
targets for Alzheimer disease. Thus, the primary goal of this proposal is to integrate comprehensive
genomic analysis of the combined ADSP data (WGS, WES, SNP array) with extant biological data to
identify the highest priority variants and loci as candidates for downstream functional analysis. By
leveraging the data derived from the AA and HI admixed populations, we use their increased diversity to
accelerate and define likely targets. This goal will be met by: 1) Characterizing genomic variation in LOAD using
ethnically diverse datasets. We will supplement the ADSP-DEP and ADSP-FUS with additional, separately
funded WES and WGS data; 2) enhancing discovery and fine-mapping using admixture analyses in ethnically
diverse datasets; and 3) Prioritizing variants and genes by integrating statistical and biological information. For
the variants we identify, we will generate additional information from structural and gene expression data and
integrate all data into a genomically driven comprehensive biological network that will be used to prioritize loci
for functional testing as therapeutic targets.

## Key facts

- **NIH application ID:** 10242911
- **Project number:** 5U01AG058654-04
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** William S Bush
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,886,114
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242911

## Citation

> US National Institutes of Health, RePORTER application 10242911, The Alzheimer Disease Sequence Analysis Collaborative (5U01AG058654-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242911. Licensed CC0.

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