# Genetic Epidemiology and Multi-Omics Analyses in Familial and Sporadic Alzheimer's Disease Among Secular Caribbean Hispanics and Religious Order

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $2,385,628

## Abstract

ABSTRACT
 For 25 years, we have investigated the genetic bases of familial and sporadic Alzheimer’s disease (AD)
among Caribbean Hispanics in the US and in the Dominican Republic, contributing samples and data to the
Alzheimer’s Disease Genetics Consortium and the Alzheimer’s Disease Sequencing Project. For this new
proposal, we intend to integrate the genetic analyses of AD in Caribbean Hispanics with deep molecular
phenotyping: epigenomics, transcriptomics, proteomics and metabolomics using whole blood, plasma,
cerebrospinal fluid and brain tissue where possible. Multi-omics data generated in this minority population will
be used to understand the effects of gene variants on disease, clarify the affected proteins and pathways that
underlie AD and for comparison to results obtained from similar studies in white, non-Hispanic populations such
as Accelerated Medicines Partnership – Alzheimer’s Disease.
 Compared with non-Hispanics, we have shown that Caribbean Hispanics are three times more likely to
develop AD by age 75 years. If they have family members with AD their risk is five times higher. From the study
entitled, “Estudio Familiar Investigar Genetica de Alzheimer” (EFIGA, RF1AG01543) we have clinical information
and biological samples in 701 families multiply affected by AD, including 5,932 individuals of which 304 families
(43%) have three or more affected relatives and 1,874 individuals with sporadic AD and 2,739 healthy controls.
We have begun recruiting members of the Caribbean Hispanic Religious Orders aged 60 years and older who
consent to blood sampling for DNA and plasma, lumbar puncture for cerebrospinal fluid and autopsy at death.
Our systematic genetic analyses in CH have yielded putative variants in ABCA7, BIN1, CD2AP, CLU, CR1,
EPHA1, MS4A4A/MS4A6A, PICALM, SORL1, PINX1 and SRCAP, each of which has been replicated.
 To covert these genetic findings into meaningful applications to AD we now want to focus our efforts on
the relationships between the genetic variants and epigenomics, transcriptomics, proteomics, metabolomics.
From the existing cohorts of genetically characterized individuals we will assemble a new multi-omics cohort.
This multi-omics cohort of 1,000 individuals will identify systems-level alterations in AD and will provide insight
into the mechanisms underlying genetic variants, assist in identifying disease pathways, putative protein-protein
interactions and downstream metabolites that can be used to inform preclinical work, develop biomarkers and
eventually therapeutic targets for drug discovery. The overarching goal is to use a genetic variant-centered,
environmentally inclusive integration of multiple omics layers to identify specific causal genes and investigate
how they may perturb pathways leading to disease.

## Key facts

- **NIH application ID:** 10812465
- **Project number:** 5R01AG067501-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** RICHARD P MAYEUX
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,385,628
- **Award type:** 5
- **Project period:** 2020-06-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10812465

## Citation

> US National Institutes of Health, RePORTER application 10812465, Genetic Epidemiology and Multi-Omics Analyses in Familial and Sporadic Alzheimer's Disease Among Secular Caribbean Hispanics and Religious Order (5R01AG067501-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10812465. Licensed CC0.

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