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Epigenetic Clock Analysis in Children With Fetal Alcohol Spectrum Disorder
Satoshi Okazaki1, Ikuo Otsuka1, Yutaka Shinko1
1From, Department of Psychiatry, (SO, IO, YS, THo, THi, NY, IS, AH), Kobe University Graduate School of Medicine, Kobe, Japan.
Insights
Children with Fetal Alcohol Spectrum Disorder (FASD) show accelerated biological aging, specifically with the GrimAge epigenetic clock. This finding highlights potential early health risks associated with FASD.
Area of Science:
- Epigenetics
- Developmental Biology
- Gerontology
Background:
- Fetal Alcohol Spectrum Disorder (FASD) presents significant health challenges, including high mortality rates, particularly in infancy.
- Existing research suggests a link between FASD and altered DNA methylation patterns.
- The study hypothesizes accelerated biological aging in individuals with FASD.
Purpose of the Study:
- To investigate whether children with FASD exhibit accelerated biological aging.
- To utilize epigenetic clocks, specifically DNA methylation profiles, to assess biological age.
- To compare epigenetic age measures between children with FASD and control groups.
Main Methods:
- Analysis of 4 independent DNA methylation datasets (buccal and blood samples).
- Evaluation of 5 DNA methylation-based epigenetic age measures: HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge.
- Assessment of telomere length (DNAmTL) as an additional aging biomarker.
Main Results:
- Children with FASD demonstrated accelerated GrimAge in one buccal and two blood datasets.
- No significant differences were observed for other epigenetic age measures or DNAmTL.
- Meta-analyses confirmed accelerated GrimAge in blood samples, but not buccal samples.
Conclusions:
- This research provides novel evidence for accelerated epigenetic aging in children diagnosed with FASD.
- The findings suggest GrimAge as a sensitive biomarker for biological aging acceleration in FASD.
- Further research is warranted to explore the clinical implications of accelerated epigenetic aging in FASD.
Background:
Fetal alcohol spectrum disorder (FASD) is characterized by severe clinical impairment, considerable social burden, and high mortality and morbidity, which are due to various malformations, sepsis, and cancer. As >50% of deaths from FASD occur during the first year of life, we hypothesized that there is the acceleration of biological aging in FASD. Several recent studies have established genome-wide DNA methylation (DNAm) profiles as "epigenetic clocks" that can estimate biological aging, and FASD has been associated with differential DNAm patterns. Therefore, we tested this hypothesis using epigenetic clocks.
Methods:
We investigated 5 DNAm-based measures of epigenetic age (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge) and telomere length (DNAmTL) using 4 independent publicly available DNAm datasets; 2 datasets were derived from buccal epithelium, and the other 2 datasets were derived from peripheral blood.
Results:
Compared with controls, children with FASD exhibited an acceleration of GrimAge in 1 buccal and 2 blood datasets. No significant difference was found in other DNAm ages and DNAmTL. Meta-analyses showed a significant acceleration of GrimAge in the blood samples but not in the buccal samples.
Conclusions:
This study provides novel evidence regarding accelerated epigenetic aging in children with FASD.
