ABSTRACT
The Alzheimer’s Disease Sequencing Project (ADSP) is a national sequencing initiative focused on identifying
genetic risk factors for AD. The project’s discovery phase includes whole exome sequencing (WES) of 10,061
unrelated non-White Hispanic individuals of European ancestry (NHW-EA) cases (N=5,096) and controls
(N=4,965), and whole genome sequencing (WGS) of 584 NHW and Hispanic/Latino (HL) familial samples. The
'Discovery Extension Phase' of the project added WGS on ~430 additional familial samples. The ADSP Follow-
Up Study 1.0 (ADSP-FUS 1.0) Phase focused on examining candidate variants from the discovery phase, and
identification of novel variants through combined analysis of diverse datasets, is ongoing. Its aim is to sequence
existing cohorts with unrelated AD cases that 'encompass the richest possible ethnic diversity' as well as highly
valuable set of autopsy confirmed cases and controls. In total we have already included in FUS over 50,000
samples for sequencing including >4,700 autopsy confirmed cases and controls, >9,400 HL ancestry cases and
controls and > 8,300 African Ancestry (AA) cases and controls. In this ADSP-FUS 2.0 application, which focuses
on the PAR-21-212 goal to increase diversity cohorts in the ADSP with WGS, we are proposing sequencing,
QC and phenotype harmonization of an additional ~16,000 individuals (~12,000 HL ancestry, 500 autopsied
NHW-EA, ~3,400 AA and ~170 Asian ancestry individuals) that will both increase our power to find effects and
will also enhance our ability to find genetic effects in underserved groups. Additionally, these datasets will
become an invaluable resource for the AD research community at-large.
