Persistent variations of blood DNA methylation associated with treatment exposures and risk for cardiometabolic outcomes in long-term survivors of childhood cancer in the St. Jude Lifetime Cohort

摘要

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