# Life Course Determinants of Epigenetic Age Acceleration and Subsequent Dementia

> **NIH NIH R00** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $248,767

## Abstract

PROJECT ABSTRACT
 This proposal seeks to understand the impact of interactions between socioeconomic status (SES),
genotype, and health behaviors on disparities in epigenetic age acceleration and cognitive decline or
Alzheimer's disease. Under the guidance of primary mentor Dr. Sharon Kardia, the training and research plan
will build upon Dr. Schmitz's expertise in health economics and genetic epidemiology to prepare her for an
independent career that integrates social science, genetics, and epigenetics into aging research. The PI will
pursue a program of training in epigenetics at the University of Michigan's School of Public Health that will
advance her knowledge and skills in (1) epigenomic biology, (2) bioinformatics and related general
programming, and (3) preprocessing and analysis of DNA methylation (DNAm) microarray data.
 The proposed research plan will capitalize on a large sample of epigenome-wide data from the Health
and Retirement Study (HRS) (N=4,000) to construct measures of DNAm age in whole blood and test for
associations with known genetic, social, and behavioral mechanisms of aging and cognitive decline or
Alzheimer's disease. DNAm age been shown to predict age with high accuracy, and studies have linked
positive deviations between DNAm age and chronological age (i.e. epigenetic age acceleration (age)) with
age-related diseases and mortality, suggesting that epigenetic processes may play a role in healthy aging.
However, few studies have investigated pathways between age and SES, and to date no study has evaluated
whether the relationship between age and SES is moderated by genetic influences or mediated by risky health
behaviors. This work builds on Dr. Schmitz's prior HRS research that used whole-genome polygenic scores
(PGSs) and objective measures of the social environment to examine the effect of gene-environment
interactions on physical health and cognitive function at older ages.
 During the K99 phase, Dr. Schmitz will construct measures of DNAm age in the HRS to test for
associations between age and disadvantaged SES, risky health behaviors, and demographic characteristics
using longitudinal moderation-mediation methods. During the R00 phase, Dr. Schmitz will incorporate PGSs
into the analyses to assess whether genetic propensity for educational attainment or cognition moderates the
relationship between SES, age, and subsequent declines in cognitive function and incidence of dementia or
Alzheimer's disease. Comparative analyses will be conducted in an African American oversample (Nൎ1,000).
R00 research will employ instrumental variables (IV) and dynamic panel methods to draw stronger claims
regarding causality. Following these analyses, replication of main findings will be pursued in multi-ethnic
cohorts that have comparable genetic, epigenetic, and social data. Results from this research program may
shed light on the specific social and biological mechanisms that underpin the SES-mortality gradient.

## Key facts

- **NIH application ID:** 10001413
- **Project number:** 5R00AG056599-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Lauren Lucia Schmitz
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,767
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001413

## Citation

> US National Institutes of Health, RePORTER application 10001413, Life Course Determinants of Epigenetic Age Acceleration and Subsequent Dementia (5R00AG056599-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001413. Licensed CC0.

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