GLASS-AD: Global Latinos Sequencing Study for Alzheimer's Disease - ABSTRACT. Hispanics/Latinos (“HL”, genetically admixed of European [EU], African [AF] and Native American
[NA] ancestry) show higher prevalence and incidence of Alzheimer's disease (AD) compared to non-Hispanic
Whites. Numbers of HL and other admixed groups in the US remain insufficient to provide statistical
significance in identifying risky and protective genetic variants, especially if rare. To this end, we introduce our
study: Global LAtinos Sequencing Study for AD (“GLASS-AD”). We will contribute to generate necessary
numbers for rare variants (RV) discovery in HL phenotyped for AD. Our proposal responds to the
Alzheimer’s Disease Sequencing Project (ADSP) Follow-Up Study 2.0 (PAR 21-212) FOA, which urges to ensure
appropriate representation of diverse populations in genetic studies of AD by leveraging existing cohorts and/or
planning new recruitment to obtain sufficient sample sizes and power. In this study we will generate new whole
genome sequencing data (WGS) in 6,000 HL: N=4,000 as part of our recently funded study “Recruitment and
Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP” (READD-ADSP AG074865) and
N=2,000 newly recruited individuals from Peru and Bolivia, leveraging the established local networks of two
ongoing recruitment studies (R56AG069118; R01AG070864). GLASS-AD, together with other independent HL
cohorts, will ultimately provide us with a large set of individuals with wide range of ancestry proportion, particularly
for NA ancestry (8% in Caribbean Hispanics, ~50% in Mexicans, 70% in Peruvian mestizos, >90% in Peruvian
and Bolivian indigenous groups). Importantly, we will increase representation of samples with substantial
NA ancestry, which are needed because currently underrepresented compared to samples with predominant
African ancestry (e.g., African Americans, Caribbean Hispanics). In addition to new recruitment and WGS data,
we will I) generate AD-biomarkers (Aβ42, tau proteins etc.) in the 2,000 Peruvians/Bolivians and II) conduct a
follow-up visit in a subset of healthy controls and mild cognitive impairment recruited by GLASS-AD in
Peru/Bolivia (N=1,000) and READD-ADSP (N=1,000) at ~3 years from initial visit to assess clinical progress.
We will also elucidate the association between AD and collected risk factors (cognition, health conditions and
behaviors, blood biomarkers) cross-sectionally and longitudinally and perform traditional and innovative RV
analyses. GLASS-AD is fully integrated with major ADSP consortia: samples will be deposited at the National
Cell Repository for Alzheimer's Disease (NCRAD), genetic data will be quality controlled and harmonized
following Genome Center for Alzheimer's Disease (GCAD) guidelines, deposited and shared by NIA Genetics of
Alzheimer’s Disease Data Storage Site (NIAGADS). GLASS data will be shared with the ADSP Follow-Up Study
(“FUS” AG057659, AG062943 and AG076482), which is sequencing several independent HL cohorts and will
ensure the largest collection of HL with WGS data. Importantly, our analyses methods will be harmonized with
ongoing ADSP analyses consortia (e.g. Collaborative for Alzheimer’s Disease Research [CADRE]).
