Genetically predicted anti‑rubella virus IgG levels and dermatitis risk: A two‑sample Mendelian randomization study

Dermatitis is a common inflammatory skin condition with multifactorial origins. Although immune responses following vaccination or natural infection have been linked to dermatological outcomes, the causal significance of virus-specific immune markers remains unclear. This study used Mendelian randomization (MR) to investigate whether genetically predicted virus-specific IgG levels are associated with dermatitis risk.

A two‑sample MR analysis was performed using genome‑wide association study (GWAS) summary statistics for IgG levels against eight common viral antigens from the Milieu Intérieur cohort and dermatitis outcomes (allergic contact dermatitis, atopic dermatitis, and other contact dermatitis) from large European cohorts. The inverse variance weighted method was used as the primary analysis method, complemented by MR‑Egger, weighted median, weighted mode, MR‑PRESSO, and leave‑one‑out sensitivity analyses.

Genetically predicted anti-rubella virus IgG levels showed a suggestive association with a lower risk of allergic contact dermatitis (OR = 0.60, 95% CI: 0.41-0.88, P = 0.009). This association did not survive Bonferroni correction and should be interpreted cautiously as such. No significant associations were observed for other virus-specific IgG levels or dermatitis outcomes. Sensitivity analyses indicated no evidence of horizontal pleiotropy or influence from any single genetic variant.

This MR study provides suggestive evidence that genetically predicted anti-rubella IgG levels may be associated with reduced allergic contact dermatitis risk. However, the findings are exploratory, do not distinguish between vaccine-induced and infection-induced immunity, and require replication and mechanistic validation. No causal associations were found for other virus-specific IgG traits.