An epigenetic component of type 2 diabetes and other diseases in humans is widely hypothesized but lacks adequate empirical support. Animal studies show that nutritional interventions during pregnancy can impact gene-specific DNA methylation in the offspring causing obesity and hypertension. We have also described persistent epigenetic changes in humans at age 58 after prenatal exposure to the Dutch Hunger Winter famine of1944-1945 and observed an increase in obesity and diabetes and other adverse outcomes. This study hopes to clarify the biologic mechanism that can link these observations in a study of 628 men and women with prenatal famine exposure and unexposed controls, arranged in 314 same-sex sibling pairs. First we will generate a genome-wide catalog of Prenatally-induced Differentially Methylated Regions (P-DMRs), comparing DNA methylation profiles for all study subjects using the novel Illumina high-throughput, high content methylation chip covering over 450k CpG sites. Then we will identify in a human cadaver tissue bank the P-DMRs subsets that mark methylation in metabolically active tissues and organs. These P-DMRs will then be evaluated in relation to prenatal famine exposure and adult disease. This approach will provide further insights into the link between the prenatal environment with adult disease.

Public Health Relevance

In this study we will utilize the unique quasi-experimental setting of the Dutch Hunger Winter to discover prenatally induced DNA methylation profiles that predict the risk of metabolic disease in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG042190-03
Application #
8526344
Study Section
Special Emphasis Panel (ZRG1-GGG-H (50))
Program Officer
Guo, Max
Project Start
2011-09-30
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2013
Total Cost
$263,965
Indirect Cost
$59,202
Name
Columbia University (N.Y.)
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Tobi, Elmar W; Goeman, Jelle J; Monajemi, Ramin et al. (2014) DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun 5:5592
Li, Zhigang; McKeague, Ian W; Lumey, Lambert H (2014) Optimal design strategies for sibling studies with binary exposures. Int J Biostat 10:185-96
Mill, Jonathan; Heijmans, Bastiaan T (2013) From promises to practical strategies in epigenetic epidemiology. Nat Rev Genet 14:585-94