# Genomic Characterization of Alzheimer Disease Risk in Admixed Populations with Native American and Southern European Genetic Ancestry

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $2,252,057

## Abstract

ABSTRACT
Alzheimer disease (AD) is the leading cause of dementia in older adults and occurs in all ethnic and racial groups.
Genetic studies of AD have mostly been performed in non-Hispanic Whites (NHW) of Northern European (NE)
ancestry. Only recently have efforts in AD started to expand into other populations, such as African-Americans
(AA) and Hispanics (HI), and have a ready demonstrated differences in both risk effect size (e.g., APOE in AA
and HI) and risk loci (e.g., ABCA7 in AA). Further evaluation demonstrates that genetic ancestry (as opposed to
environmental/cultural factors) likely underlie at least part of this heterogeneity. Individuals with the Amerindian
(AI) ancestry remain one of the most underrepresented groups in AD. Importantly, the NHW datasets did not
differentiate among the Europeans (EU), whereas recent investigations showed that these pan-European results
only partially overlap with the findings from populations from the Iberian Peninsula (IP) with Southern European
(SE) ancestry. Caribbean and South American Hispanic populations are admixed with both AI and SE, thus
making their study a critical scientific objective. Our proposed study enables testing the generalization of findings
from NHW to these other ancestries, as well as identify AD risk/protective factors correlated specifically with AI
and SE ancestry. Our results will allow for a better and more complete understanding of the genetic architecture
of AD which will help improve disease prediction, prevention, diagnosis, and treatment in AI, admixed Hispanic
populations, and beyond. To accomplish these goals, we propose three aims. In Aim 1 we will characterize
known AD loci in admixed populations with AI and SE ancestry. This includes expanding collections, generalizing
known AD loci to AI/SE populations, and variant discovery through admixture mapping and fine-mapping. In Aim
2 we will extend our Puerto Rican dataset by expanding PR multiplex families. This will allow more powerful
linkage analyses, longitudinal neurocognitive and biomarker data, and the initiation of a brain donation program.
Finally, in Aim 3 we will perform functional follow-up of variants using bioinformatics approaches, assessment of
AD biomarkers, and assessment of cellular function using IPSc.

## Key facts

- **NIH application ID:** 10335250
- **Project number:** 5R01AG070864-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Gary Wayne Beecham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,252,057
- **Award type:** 5
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335250

## Citation

> US National Institutes of Health, RePORTER application 10335250, Genomic Characterization of Alzheimer Disease Risk in Admixed Populations with Native American and Southern European Genetic Ancestry (5R01AG070864-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10335250. Licensed CC0.

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