TY - JOUR
T1 - Expression Quantitative Trait Methylation Analysis Identifies Whole Blood Molecular Footprint in Fetal Alcohol Spectrum Disorder (FASD)
AU - Krzyzewska, Izabela M.
AU - Lauffer, Peter
AU - Mul, Adri N.
AU - van der Laan, Liselot
AU - Yim, Andrew Y. F. Li
AU - Cobben, Jan Maarten
AU - Niklinski, Jacek
AU - Chomczyk, Monika A.
AU - Smigiel, Robert
AU - Mannens, Marcel M. A. M.
AU - Henneman, Peter
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/4/1
Y1 - 2023/4/1
N2 - 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.
AB - 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.
KW - DNA methylation
KW - FASD
KW - eQTM
KW - fetal alcohol spectrum disorder
KW - gene expression
UR - http://www.scopus.com/inward/record.url?scp=85152339052&partnerID=8YFLogxK
U2 - 10.3390/ijms24076601
DO - 10.3390/ijms24076601
M3 - Article
C2 - 37047575
SN - 1422-0067
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 7
M1 - 6601
ER -