# Epidemiological Integration of Genetic Variants and Metabolomics Profiles in Washington Heights Columbia Aging Project

> **NIH NIH RF1** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $8,710,391

## Abstract

ABSTRACT
Metabolites reflect the dynamic, qualitative and quantitative changes in humans and provide a functional
assessment of the physiological state of individuals with and without disease. The metabolome represents the
closest link between the phenotype and the underlying biochemical layers of the genome. In the human body,
metabolites are chemically transformed during metabolism in response to genetic and environmental factors in
the causal pathway to a disease or to an in vivo change as a result of the disease. The human metabolome has
been studied in Alzheimer's disease (AD) in a small number of cross-sectional and longitudinal investigations
with limited numbers of ethnic groups and little or no concurrent genetic analyses. The Washington Heights,
Inwood Columbia Aging Project is a multi-ethnic cohort that has collected clinical data and biological resources
for several years with the goal of identifying the environmental and genetic risk factors and causes of AD. The
cohort is ideally suited for this project because 23% are non-Hispanic whites, 29% are African Americans and
48% are Caribbean Hispanics, and because loss-to-follow up has been minimal due to the use of a validated
telephone interview of the participants and informants. We have conducted medical and neurological
examinations, cognitive assessments and captured environmental/lifestyle risk and protective factors in this
longitudinal investigation at 18-month intervals. We have also conducted genome wide association studies,
whole exome and genome sequencing and have stored DNA and plasma over multiple time points. We now
propose to identify those metabolites that are associated with the development of AD and that reflect changes
in disease severity over time and how they interact with environmental factors. The strength of our study lies in
its ability to investigate changes in the metabolome among a group of individuals from different ethnic and racial
backgrounds that have been genetically characterized. Blood is readily available as a means for repeated
measures augmenting the precision of individualized analyses particularly when completed in a genetically
characterized multi-ethnic cohort. We propose a genetically driven, metabolomics profile analyses from plasma
to investigate endogenous metabolites related to AD and exogenous metabolites related to
environmental/lifestyle exposures associated with AD. The planned study will provide a major opportunity to add
deeper phenotyping using metabolomics to a genetically characterized, multi-ethnic cohort residing in an urban
community, which in turn, should clarify the underlying mechanisms linking to genetic and environmental
pathways leading to AD.

## Key facts

- **NIH application ID:** 10055447
- **Project number:** 1RF1AG066107-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** RICHARD P MAYEUX
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $8,710,391
- **Award type:** 1
- **Project period:** 2020-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055447

## Citation

> US National Institutes of Health, RePORTER application 10055447, Epidemiological Integration of Genetic Variants and Metabolomics Profiles in Washington Heights Columbia Aging Project (1RF1AG066107-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10055447. Licensed CC0.

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