Location: Children's Nutrition Research Center
Project Number: 3092-51000-062-40-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Oct 20, 2015
End Date: Mar 31, 2019
Objective 1. Use genome-wide technologies to identify genomic and epigenomic markers associated with clinically relevant manifestations in severe childhood malnutrition (SCM). Sub-objective 1A: Compare genome-wide DNA methylation in two cohorts of edematous SCM (ESCM) cases and non-edematous SCM (NESCM) controls. Sub-objective 1B: Perform genome-wide genotyping on ESCM cases and NESCM controls. Objective 2. Integrate genome-wide DNA methylation, as an intermediate phenotype of SCM manifestations, with cis-sequence variation, in order to identify causal genes and pathways in SCM outcomes. Objective 3. Determine whether epigenetic markers can be used as surrogate biomarkers of SCM phenotypes. Objective 4. Examine the feasibility of providing dietary enhancers of DNA methylation to improve outcome differences in SCM.
Previous studies have observed significant metabolic differences between ESCM and NESCM in the major pathway contributing to DNA methylation, suggesting that genome-wide, levels of DNA methylation may differ between the two groups, possibly as a result of genetic variation. This research project will use genome-wide assessments to identify genomic and epigenomic- differences between SCM phenotypes and integrate these differences using advanced statistical models in order to identify gene variants that causally contribute to outcome differences. The project will also evaluate the ability of methylation levels to categorize SCM phenotypes and assess the potential long-term molecular effects of nutrient stress. The study will also create a framework for evaluating methyl-group supplementation in SCM.