16 CpG Sites in DNA at Birth Linked to Early-Onset Atopic Dermatitis

A study found distinct cord-blood DNA methylation (DNAm) patterns are associated with a risk of early-onset atopic dermatitis by 2 years old.1 The research will be presented at the 2025 American Academy of Allergy, Asthma, & Immunology (AAAAI) annual meeting in San Diego from February 28 – March 3.

According to the Allergy & Asthma Network, approximately 9.6 million children live with atopic dermatitis, leading to significant health, financial, and social burdens.2 Studies have shown that DNAm is linked to atopic dermatitis, but investigators recognized the need for research on whether the role of DNAm at birth could predict early-onset atopic dermatitis.3 Investigators, led by Amy Eapen, MD, from Henry Ford Health System, sought to characterize cord-blood DNAm in participants with and without early-onset atopic dermatitis by 2 years old.1

The team analyzed DNA from the umbilical cord blood of 302 newborns in a longitudinal study in Wayne County called WHEALS. They used a special genetic tool, the Asthma & Allergy array, to look for specific DNA changes in the epigenome that might be linked to early-onset atopic dermatitis. In their epigenome-associated study (EWAS), investigators identified CpG sites in the DNA associated with early-onset atopic dermatitis.

Eapen and colleagues used the statistical method combp to find differentially methylated regions within a 1 kb range. They created a poly-CpG score to predict early-onset atopic dermatitis by selecting the most relevant CpG sites using elastic net penalized logistic regression.

In total, there were 75 cases of early-onset atopic dermatitis and 227 control cases with no atopic dermatitis. The study revealed that 16 differentially methylated regions were associated with early-onset atopic dermatitis.

After identifying CpG sites linked to early-onset atopic dermatitis, investigators examined biological pathways. They saw that affected genes were involved in T-cell receptor signaling, MHC class II antigen presentation, and IFN-gamma signaling. These findings indicate that immune system activity may be a key factor in early-onset atopic dermatitis.

Moreover, for the poly-CpG score, 1275 CpG sites initially showed some association with early-onset atopic dermatitis (P < .01). A total of 180 CpG sites were selected for the final predictive model.

The study ultimately suggested out of all the identified DNA sites, 180 were the most important for predicting early-onset atopic dermatitis. The poly-CpG score also demonstrated high predictability of early-onset atopic dermatitis with an area under the receiver operator characteristic curve of 93.7% (sensitivity: 84.9%, specificity: 86.3%).

“Differential cord-blood DNAm is associated with risk of early-onset AD by age 2,” investigators concluded. “Future studies would include larger, diverse cohorts to assess the validity of our findings.”

References

1. Eapen, A, Loveless, I, Pan, M, et al. The Impact of the Cord Blood Methylome on Early-Onset Atopic Dermatitis. Late-breaker will be presented at the 2025 AAAAI annual meeting in San Diego from February 28 – March 3.

2. Eczema (Atopic Dermatitis) Statistics. Allergy & Asthma Network. https://allergyasthmanetwork.org/what-is-eczema/eczema-statistics/. Accessed February 12, 2025.

3. Schmidt AD, de Guzman Strong C. Current understanding of epigenetics in atopic dermatitis. Exp Dermatol. 2021 Aug;30(8):1150-1155. doi: 10.1111/exd.14392. Epub 2021 Jun 1. PMID: 34008901; PMCID: PMC8361700.