Fig. 1

Research process for identifying metabolites and inflammatory proteins causally associated with AD. Schematic diagram in the lower right corner: the design of mediation Mendelian randomization analyses. First of all, a two-sample MR was performed to investigate the causal relationships between blood metabolites (exposure) and atopic dermatitis (outcome). Secondly, inflammatory proteins (mediator) were selected for subsequent mediation analyses. And lastly, the two-step MR analysis was conducted to detect potential mediating inflammatory proteins (Step 1, the effect of blood metabolites on inflammatory proteins; Step 2, the effect of inflammatory proteins on atopic dermatitis). The instrumental variables used for MR need to satisfy 3 assumptions. First, the genetic variants must be robustly associated with blood metabolites. Second, the genetic variants must not associate with any confounders. Third, the genetic variants only affect the outcome through the exposure and not through any direct casual pathway. Abbreviations: MR, Mendelian Randomization; AD, Atopic dermatitis; SNP, Single nucleotide polymorphism; MAF, Minor allele frequency.