Fig. 3: Four significant CpGs identified by epigenome-wide meta-analysis and their associations with biological endophenotypes and clinical outcomes across cohorts.

Meta-Analysis: (A) Manhattan plot (N = 226). The horizontal solid line (dark red) indicates P = 9.0E-08, and the dashed line (gray) indicates P = 1.0E-06. The four probes that reached q-value significance are highlighted in light green and labeled with their corresponding gene names. For details on the overall quality of the genome-wide analysis—including Q-Q plots and genomic inflation factors—see Supplementary fig. S2. B Forest plot for the four significant probes. Error bars represent the SEM. Judicial Autopsy Cases: (C) Correlation plot for cg23172545_SERPINB9P1 showing its relationship to the thymus weight ratio (r = 0.57, P = 0.02). Adolescent Brain Imaging: (D) Correlation plots for cg04794662_FOXP1 (R.OFrC: r = 0.31, P = 5.4E-04; L.MPCG: r = 0.27, P = 0.003; L.OFuG: r = −0.27, P = 0.003), cg05646433_CHST11 (R.OFrC: r = 0.20, P = 0.03; L.OFuG: r = −0.20, P = 0.03) and cg02564536_ATE1 (R.OFrC: r = −0.24, P = 0.008) with each of the GMV measures in these regions. Refer to Supplementary Table S11 for detailed statistical analyses. Toddler Social Cognition and Adolescent Brain Imaging: (E, F) Correlation plots illustrating associations between methylation levels and clinical measures (SDQ and DSRS-C). Toddler cohort: cg02564536_ATE1 (SDQ: r = −0.31, P = 0.007) and cg23172545_SERPINB9P1 (SDQ: r = −0.29, P = 0.011) showed significant correlations. Adolescent cohort: cg05646433_CHST11 correlated significantly with both SDQ (r = 0.32, P = 0.0003) and DSRS-C (r = 0.42, P = 3.0E-06). Additionally, cg02564536_ATE1 showed a significant negative correlation with SDQ (r = −0.26, P = 0.0045), and cg04794662_FOXP1 showed marginally significant positive correlations with SDQ (r = 0.17, P = 0.058) and DSRS-C (r = 0.18, P = 0.053).