Fig. 5: eQTM analysis linking mediator CpGs to gene expression.

a Number of CpGs associated with both CMRFs and treatments that were identified as eQTMs (N = 199 survivors). b Scatter plot showing the association between DNAm at cg20370568 and ANTXR2 expression (N = 191 survivors). The solid line represents the ordinary least-squares linear regression fit, and the shaded band indicates the 95% confidence interval of the fitted mean. Pearson correlation coefficients and two-sided p-values are shown. c Mediation diagram showing cg20370568 partially mediates the effect of body-trunk-RT on abnormal glucose (N = 191 survivors), with a 20.3% proportion of the effect mediated. Mediation was assessed using regression-based mediation analysis with two-sided hypothesis testing, in which path a was estimated using linear regression of the CpG mediator on treatment, path b using logistic regression of abnormal glucose on the CpG mediator conditional on treatment, and paths c and c’ using logistic regression models of abnormal glucose on treatment without and with adjustment for the mediator, respectively. Path coefficients (a, b, c, c’), effect estimates, and exact p values are shown in the schematic. d Stratified scatter plots showing the association between cg20370568 DNAm and ANTXR2 expression among survivors exposed or unexposed to body-trunk-RT (N = 191 survivors). Solid lines represent ordinary least-squares linear regression fits and shaded bands indicate the 95% confidence intervals of the fitted means. Pearson correlation coefficients, two-sided p-values, and sample size (N) for each group are shown. Source data are provided as a Source Data file. CMRF cardiometabolic risk factor, RT radiotherapy, TPM transcripts per million.