Fig. 1

Statistical analysis workflow. Abbreviations: CHC, chronic health condition; EWAS, epigenome-wide association study; HTG, hypertriglyceridemia. ^aLinear regression model was adjusted for covariates including sex, age, other cancer treatment exposures, leukocyte subtype proportions, top three genetic principal components, and top four methylation principal components. ^bLogistic regression model was adjusted for covariates including sex, age, and CHC-specific polygenic risk score. ^cResidual of M-value was calculated based on linear regression adjusted for covariates including sex, age, leukocyte subtype proportions, significant genetic principal components, and methylation principal components. ^dMediation analysis included two regression modes: a logistic regression model with CHC status as an outcome, specific treatment as treatment variable (term used for the exposure in the Mediation R package), residual M-value for a CpG site as a mediator variable and adjusted for age, sex, CHC-specific polygenic risk score, and other cancer treatment exposures; a linear regression model with residual M-value for a CpG site as an outcome, specific treatment as treatment variable and other significant treatments as covariates. ^eMediation analysis as above except for replacing residual M-value for a CpG site with a combined methylation score by summing up the residual M-values for multiple CpG sites that were found to be significant mediators individually