Researchers analyzed data from nearly 280,000 individuals of European ancestry across 26 population cohorts. They examined interactions between 24 genetic variants associated with eczema and 18 early-life environmental exposures, including pet ownership, smoking, antibiotic use, and breastfeeding.
One variant—rs10214237, located near the IL7R gene on chromosome 5p13.2—stood out. The T allele increased eczema risk only in individuals not exposed to dogs during infancy. Among those exposed to dogs, the genetic risk wasn't observed.
In individuals without dog exposure, the T allele was linked to a 14% increased risk of eczema (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.08–1.22). Among those exposed to dogs early in life, the risk was neutral (OR = 0.99, 95% CI = 0.93–1.05). This gene-environment interaction was statistically significant in both the discovery and replication phases.
To explore the underlying biology, the researchers conducted lab experiments using human keratinocytes. Cells with the T:T genotype at rs10214237 showed higher IL7R mRNA expression and increased levels of immune signaling molecules such as CXCL8, CSF2, and CCL2 when exposed to dog epithelial extract.
These molecules are involved in interleukin-10 signaling, a pathway known to suppress inflammatory skin responses. The findings suggested that dog allergen exposure may activate protective immune responses in genetically susceptible individuals.
A similar trend was observed with exposure to older siblings, though replication lacked sufficient statistical power.
The researchers also investigated other exposures—cat ownership, tobacco smoke, breastfeeding, and washing practices—but none of them showed consistent interaction with genetic variants. Previously reported interactions between FLG mutations and cat exposure weren't confirmed, despite the adequate power to detect them.
The researchers noted that most environmental factors examined had limited or no interaction with genetic risk, suggesting that strong gene-environment interactions in eczema may be uncommon and population-specific.
The researchers' focus on individuals of European ancestry may have limited generalizability to other populations. Another limitation was the lack of detailed environmental data such as specific washing products used in infancy.
Despite these limitations, the findings offered new evidence that early-life exposures—particularly dog ownership, may modify genetic risk for eczema through immune mechanisms in the skin. Further studies in diverse populations are needed to confirm these results and clarify how environmental factors influence eczema development.
Full disclosures can be found in the published study.
Source: Allergy