Expression Quantitative Trait Methylation Analysis Identifies Whole Blood Molecular Footprint in Fetal Alcohol Spectrum Disorder (FASD)

Fetal alcohol spectrum disorder (FASD) encompasses neurodevelopmental disabilities and physical birth defects associated with prenatal alcohol exposure. Previously, we attempted to identify epigenetic biomarkers for FASD by investigating the genome-wide DNA methylation (DNAm) profiles of individuals with FASD compared to healthy controls. In this study, we generated additional gene expression profiles in a subset of our previous FASD cohort, encompassing the most severely affected individuals, to examine the functional integrative effects of altered DNAm status on gene expression. We identified six differentially methylated regions (annotated to the SEC61G, REEP3, ZNF577, HNRNPF, MSC, and SDHAF1 genes) associated with changes in gene expression (p-value < 0.05). To the best of our knowledge, this study is the first to assess whole blood gene expression and DNAm-gene expression associations in FASD. Our results present novel insights into the molecular footprint of FASD in whole blood and opens opportunities for future research into multi-omics biomarkers for the diagnosis of FASD.