Fig 1.
The orange boxes and arrows represent the forward MR analyses, with psoriasis as the exposure and AD as the outcome, while the cyan boxes and arrows represent the reverse MR analyses, with AD as the exposure and psoriasis as the outcome. Abbreviations: MR, Mendelian randomization; AD, atopic dermatitis; SNPs, single-nucleotide polymorphisms.
Table 1.
Primary information of the utilized consortia and data.
Fig 2.
MR to identify the causal impact of genetically predicted psoriasis on the risk of AD.
(A) Scatter plots of the genetic effects of IVs on the genetic predisposition to psoriasis and the subsequent risk of AD. The slope of the straight lines with different colors indicates the causal estimate in the corresponding methods of MR. Each black dot corresponds to an IV included in MR, whereas the gray bars represent the SDs of the genetic effect estimations. (B) Forest map of the visualized causal influences of each included SNP on the risk of AD risk. (C) “Leave-one-out” plots of the causal relationship between psoriasis and AD. (D) Causal effect of psoriasis on AD visualized in a forest map using five methods. Abbreviations: AD, atopic dermatitis; MR, Mendelian randomization; IVs, instrument variables; SD, standard deviation.
Fig 3.
SNP-mapped genes and NOS2-related molecular pathways. (A) SNP-to-gene mapping displaying the genes associated with the forward SNPs, both of which are labeled in the figure. (B) Pathway analysis demonstrating the biological mechanism related to the NOS2 gene. Abbreviations: SNP, single-nucleotide polymorphism; NOS2, nitric oxide synthase 2.
Fig 4.
MR of the causal estimates of the effects of genetic predisposition to AD on the risk of psoriasis. (A) Scatter plots of the effects of IVs on the genetic predisposition to AD and the subsequent risk of psoriasis. The slope of the straight lines in different colors indicates the causal estimation in the corresponding methods of MR. Each black dot corresponds to an IV included in MR, whereas the gray bars represent the SD of the estimation of the genetic effect. (B) Forest map of the visualized causal influence of each included SNP on the risk of psoriasis. (C) “Leave-one-out” plots of the causality between AD and psoriasis. (D) Causal impact of AD on the risk of psoriasis visualized as a forest map of the five methods. Abbreviations: MR, Mendelian randomization; AD, atopic dermatitis; IVs, instrument variables; SD, standard deviation.
Fig 5.
A possible model of the mechanism linking NOS2 expression to the development of psoriasis.
A variety of activators such as cytokines, microbial products, and immune complexes, stimulate cellular NOS2 expression in keratinocytes. The formed •NO then induces inflammation, angiogenesis stimulation, lipid peroxidation, keratinocyte proliferation, and other effects through interactions with other superoxide moieties. In this process, NOS2 protein expression is not fully correlated with its mRNA expression because NOS2 protein translation can be inhibited by various factors (e.g., miR-31, arginase 1).