# Development of a DNA methylation data resource for exposome research on Alzheiemer's Disease and Related Dementias within the Dutch Hunger Winter Families Study

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $474,336

## Abstract

SUMMARY
The roots of Alzheimer’s Disease (AD) and AD-Related Dementias (ADRD) extend backward in development
to the earliest stages of life. Perinatal insults and intra-uterine growth restriction are linked to increased risk for
several AD/ADRD risk factors, including obesity, type 2 diabetes mellitus, and cardio-metabolic disease, and
therefore represent a crucial feature of the AD/ADRD exposome. The mechanisms mediating these perinatal-
insult effects are hypothesized to operate through epigenetic changes involving DNA methylation. However,
isolating the causal effects of in-utero exposures from correlated risk factors, such as poverty, is challenging in
human studies. Natural experiments, including famine studies, provide a model to study causal effects of
perinatal insults on human aging and are an ideal setting in which to develop research infrastructure to study
the AD/ADRD exposome. The Dutch Hunger Winter Families Study (DHWFS) uses a sudden, war-induced
famine as a natural experiment. The famine was caused by a Nazi blockade during WWII in 1944-45. Because
the impact of famine was immediate, transient, and population-wide, DHWFS comparison of infants born
during the famine with those born before or after the famine will identify potential long-term effects of perinatal-
insults. In the parent grant to this supplement application, stored DHWFS biospecimens are being genotyped
to examine if famine effects on fertility and fetal survival could induce significant selection bias in the natural
experiment. Biospecimens are available of N=956 individuals, 37% of whom were exposed to famine in-utero
and the remainder of whom are siblings of the famine-exposed individuals and "time controls" born
immediately before or after the famine. Under this supplement application we propose new assays of stored
biospecimens to generate a new DNA methylation database for the DHWFS. We will use Illumina EPIC array
technology to assay ~850,000 CpG sites across the genome; apply published algorithms to compute a library
of exposome variables; link these data with detailed in-utero exposure and neuropsychological test data to
build an AD/ADRD exposome DNA methylation database; and develop platforms for electronic sharing of the
data with outside research teams. The proposed project will build unique infrastructure for studies of the
AD/ADRD exposome that will enable causal identification of impacts of in-utero exposure on the life-course
development of AD/ADRD risk via epigenetic mechanisms.

## Key facts

- **NIH application ID:** 10661283
- **Project number:** 3R01AG066887-03S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Daniel Walker Belsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $474,336
- **Award type:** 3
- **Project period:** 2020-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10661283

## Citation

> US National Institutes of Health, RePORTER application 10661283, Development of a DNA methylation data resource for exposome research on Alzheiemer's Disease and Related Dementias within the Dutch Hunger Winter Families Study (3R01AG066887-03S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10661283. Licensed CC0.

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