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

Abstract

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.

Genetic associations with dementia‐related proteinopathy: Application of item response theory

“… 69 , 73 Methylation of the SDHAF1 locus was specifically implicated in fetal alcohol syndrome, and mutations in the SDHAF1 gene were linked to the phenotype of white matter disease (specifically, pediatric leukoencephalopathy). 73 , 74 , 75 , 76 More work is required to ascertain if the association between SDHAF1 genetic variation and TDP‐43 pathology is robust in aging individuals.…”

Multi-Omics Data Analysis Identifies Prognostic Biomarkers across Cancers

“…The SEC61G gene was differently methylated in patients with Balkan endemic nephropathy [ 113 ]. The SEC61G gene is differentially expressed and methylated in fetal alcohol spectrum disorder patients [ 114 ]. There are many studies about relationship between the mutation in the PTDSS1 gene and Lenz-Majewski syndrome [ 115 ].…”

Associations between epigenome-wide DNA methylation and height-related traits among Sub-Saharan Africans: the RODAM study

“…All participants for the DNAm profiling were selected from a case–control design in which ∼ 300 individuals were diabetic cases, ∼300 were deemed diabetic control cases, and ∼ 135 were obese control cases). 17 The EWAS was performed using the DNAm profiles of 736 participants of the RODAM cohort, 18 of which 713 samples passed quality control. Quality control procedures were based on those described by Meeks et al 18 and Chen et al 19 Individuals missing one or more height-related traits and those whose measurements were erroneously recorded were omitted from inclusion in the final sample for this study ( n = 704).…”

“…17 The EWAS was performed using the DNAm profiles of 736 participants of the RODAM cohort, 18 of which 713 samples passed quality control. Quality control procedures were based on those described by Meeks et al 18 and Chen et al 19 Individuals missing one or more height-related traits and those whose measurements were erroneously recorded were omitted from inclusion in the final sample for this study ( n = 704).…”

“…Differential epigenetic aberrations might echo in later life without having a current functional effect, but would be involved in other traits, biological mechanisms, or co-morbidity such as cardiovascular disease. 18 Lastly, this study was conducted utilizing epigenetic profiles based on whole bloods samples, though we focused on the height-related traits determined by bone development. As DNAm is tissue-specific, and DNAm profiles derived from blood might therefore not be representative of processes occurring in bone tissue.…”