A novel DNA methylation-based surrogate biomarker for chronic systemic inflammation (Inflammation Latent Variable Methylation Surrogate, InfLaMeS)

Chronic low-grade systemic inflammation is a risk factor for chronic diseases and mortality and is an important biomarker in health research. DNA methylation (DNAm) surrogate biomarkers are valuable exposure, risk factor, and health outcome predictors in studies where the measures cannot be measured directly and often perform as well or better than direct measures. We generated a DNAm surrogate biomarker for chronic, systemic inflammation from a systemic inflammation latent variable of 7 inflammatory markers and evaluated its performance relative to measured inflammatory biomarkers in predicting several age-associated outcomes of interest, including mortality, activities of daily living, and multimorbidity in the Health and Retirement Study (HRS). The DNAm surrogate, Inflammation Latent Variable Methylation Surrogate (InfLaMeS), correlated with 7 individual inflammation markers (r = -0.2-0.6) and had similar or stronger associations with multimorbidity, disability, and 4-year mortality in HRS compared to the systemic inflammation latent variable measure when predicting multimorbidity, disability, and 4-year mortality in HRS. Findings were validated in an external cohort, the Irish Longitudinal Study of Ageing. These results suggest that InfLaMeS provides a robust alternative to measured blood-chemistry measures of inflammation with broad research applicability in instances where values of inflammatory markers are not measured but DNAm data are available.