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

Figure 4.

Figure 4

DNA methylation regulation of LGALS9 and its interaction with inflammatory cytokines in SD

(A) LGALS9 locus plots reveal consistent genetic effects across SD GWAS, cis-mQTL, and cis-eQTL datasets (p < 1 × 10−5).

(B) Three-step SMR analysis demonstrated causal relationships between DNA methylation-mediated LGALS9 gene expressions and the onset of SD (P SMR multi < 0.05; HEIDI test p > 0.01, and Cochran’s Q p > 0.05).

(C) Locus comparisons of LGALS9 gene expression and inflammatory cytokines (CD5, IL-10, and CST5) were performed via colocalization (PPH4 > 0.5).

(D) ELISA validation of serum levels of LGALS9, CD5, IL-10, and CST5 in 16 patients with SD and 16 controls. Statistical analysis: SMR criteria as in Figure 3. Data sources: eQTLGen and FinnGen R10. Colocalization: PPH4 > 0.5. ELISA: p = 0.0486 for LGALS9; ∗p < 0.05, ∗∗p < 0.01 versus controls. Boxplots show the median and IQR.