Researchers identified 77 genetic loci associated with atopic dermatitis, including 10 novel variants, according to a recent analysis.
In a genome-wide meta-analysis, published in the Journal of Investigative Dermatology, investigators examined the data of about 1.1 million participants, including 37,541 with atopic dermatitis (AD) and just under 1.1 million controls.
The investigators identified 77 AD-associated loci, including 10 not previously reported. Data were drawn from FinnGen, the Estonian Biobank, UK Biobank, EAGLE Consortium, and BioBank Japan, providing one of the largest genetic studies of AD to date.
The loci identified were enriched in immune regulatory pathways, with subgroup analyses revealing stronger genetic associations in severe AD cases compared with mild cases for 55 of the 79 tested variants. Additionally, several loci were linked to early-onset AD, with variants in the FLG locus showing the strongest association with childhood-onset disease.
The analysis also identified previously unreported loci near FOXP1, BHLHE40, and ARID3A, suggesting potential roles in immune regulation and skin barrier function. Functional analyses indicated these variants were associated with altered gene expression, including increased AQP3 expression in skin tissue and elevated MMP12 levels in the blood.
Key findings noted genetic overlap between AD and other inflammatory conditions such as inflammatory bowel disease. Enrichment analyses identified shared pathways related to immune regulation and inflammation. Replication of these findings is needed to confirm their implications.
Heritability estimates for AD based on single-nucleotide polymorphisms were approximately 7.8%, consistent with prior genome-wide association studies. Severe AD was associated with higher polygenic risk scores compared with mild AD, indicating larger genetic effect sizes in severe cases.
The study identified genetic pathways associated with immune regulation and skin barrier integrity, contributing to the understanding of AD pathophysiology. The findings suggested a greater genetic contribution in severe AD and indicated potential therapeutic targets. Replication and further exploration of these results, particularly the 10 novel loci, are warranted.
Full disclosures can be found in the published analysis.
