# Project 2: Multi-Ethnic Analysis for Alzheimer Disease

> **NIH NIH U19** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $674,840

## Abstract

PROJECT SUMMARY/ABSTRACT: PROJECT 2 (Multi-Ethnic Analysis for Alzheimer Disease)
Alzheimer's disease (AD)’s etiology is still relatively unexplained but substantial evidence supports a strong
genetic component. Most AD genetic studies have focused on European (EU) descent individuals, despite
Hispanic/Latinx (HL, genetically admixed of EU, African (AF) and Native American (NA) ancestry) and African
Americans (AA, genetically admixed of EU and AF ancestry) having higher prevalence and incidence of AD.
Thus, it is important to understand how ancestry affects AD risk among diverse populations to provide better
models of risk. Overall, we hypothesize that diverse populations harbor novel AD risk/protective alleles
that are rare or absent in other populations or that they have modifiers that alter the effects of common
risk alleles, and specifically that AF and NA ancestries enhances AD risk. ʺRecruitment and Retention for
Alzheimer’s Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP) will add new, diverse cohorts that
augment the existing pool of genomic data. To test our hypothesis, we will perform admixture mapping in AA
and HL, assuming causal variants/genes are more frequently on chromosomal segments inherited from the
ancestral population with higher AD prevalence. We will also investigate universal genetic loci (i.e. those that
confer risk in most or all populations) by performing a large trans-ethnic study that includes AA, HL, as well as
EU and AF ancestral populations. This approach will boost statistical power, detection of rare variant and
dissection of AD genetic architecture within populations. We will also test whether associating and/or modifying
loci differ from the genomic background in terms of past selective events that may have shifted AD risk. To study
the diversity of AD genetic risk, we will: 1) Determine the AF and NA origins of genetic variation in AD, using
admixed populations and investigate ethnic-specific modifiers. We will estimate global and local ancestry
in each HL and AA cohort separately, in order to investigate their association with AD and prioritize the genomic
segments where higher AF or NA ancestry confers higher AD risk. These segments will be fine-mapped
employing resources developed in Project 1 and with ancestry-aware association tests. We will also examine
whether the effects of known or newly-identified AD-associated loci are altered by ancestry background. 2) We
will perform trans-ethnic meta-analysis across AF, AA, HL, NHW cohorts using single-marker and gene-
based outputs from Project 1 but also we will meta-analyze local ancestries that are shared across admixed
cohorts (e.g. AF component across AA, Puerto Ricans, Cubans etc.). Finally, 3) we will perform explicit tests
of selection on AD-associated loci and their modifying loci prioritized by Project 1 and 2 and determine whether
patterns of evolutionary history are consistent across diverse populations with patterns of association.

## Key facts

- **NIH application ID:** 10654541
- **Project number:** 5U19AG074865-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Giuseppe Tosto
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $674,840
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10654541

## Citation

> US National Institutes of Health, RePORTER application 10654541, Project 2: Multi-Ethnic Analysis for Alzheimer Disease (5U19AG074865-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10654541. Licensed CC0.

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