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. 2026 Feb 7;29(3):114950. doi: 10.1016/j.isci.2026.114950

Figure 3.

Figure 3

DNA methylation regulation of SH2B3 expression and its interaction with inflammatory cytokines in SD

(A) SH2B3 locus plots reveal consistent genetic effects of SD GWAS, cis-mQTL, and cis-eQTL (p < 1 × 10−5).

(B) Three-step SMR analysis demonstrated causal relationships between DNA methylation-mediated SH2B3 gene expressions and the onset of SD (P SMR multi < 0.05; HEIDI test p > 0.01; Cochran’s Q p > 0.05).

(C) Locus comparisons for SH2B3 gene expression and inflammatory cytokines (CCL19, IL-2Rβ, PD-L1, and TGF-α) were performed via colocalization (PPH4 > 0.5).

(D) ELISA validation of serum levels of SH2B3, CCL19, IL-2Rβ, PD-L1, and TGF-α in 16 patients with SD and 16 controls. Statistical analysis: SMR: P_SMR_multi < 0.05, HEIDI p > 0.01, Cochran’s Q p > 0.05. Data sources: eQTLGen (N = 31,684),18 blood mQTL,19 and FinnGen R10.20 Colocalization: coloc package, PPH4 > 0.5 indicates shared causal variants. ELISA: p < 0.0001 for SH2B3; Mann-Whitney U test or independent t test for cytokines, p < 0.001. Boxplots show the median and interquartile range (IQR). All samples were assayed in duplicate.