Meier Helen C S, Klopack Eric T, Farnia Mateo P, Hernandez Belinda, Mitchell Colter, Faul Jessica D, McCrory Cathal, Kenny Rose Anne, Crimmins Eileen M
Survey Research Center, Institute for Social Research, University of Michigan.
Leonard Davis School of Gerontology, University of Southern California.
medRxiv. 2024 Oct 15:2024.10.11.24315339. doi: 10.1101/2024.10.11.24315339.
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 measure. We generated a DNAm surrogate biomarker for chronic, systemic inflammation from a systemic inflammation latent variable of seven 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 seven individual inflammation markers (r= -0.2-0.6) and performed as well or better 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 applicability in instances where values of inflammatory markers are not measured but DNAm data is available.
慢性低度全身性炎症是慢性疾病和死亡的危险因素，也是健康研究中的重要生物标志物。在无法直接测量相关指标的研究中，DNA甲基化（DNAm）替代生物标志物是有价值的暴露、危险因素和健康结果预测指标，其表现往往与直接测量指标相当甚至更好。我们从七种炎症标志物的全身性炎症潜在变量中生成了一种用于慢性全身性炎症的DNAm替代生物标志物，并在健康与退休研究（HRS）中评估了其在预测多个与年龄相关的感兴趣结局（包括死亡率、日常生活活动能力和多种疾病并存情况）时相对于实测炎症生物标志物的性能。这种DNAm替代标志物，即炎症潜在变量甲基化替代物（InfLaMeS），与七种个体炎症标志物相关（r = -0.2 - 0.6），并且在预测HRS中的多种疾病并存情况、残疾和4年死亡率时，其表现与全身性炎症潜在变量测量指标相当或更好。研究结果在外部队列爱尔兰纵向老龄化研究中得到了验证。这些结果表明，InfLaMeS为炎症的实测血液化学指标提供了一种可靠的替代方法，在未测量炎症标志物值但有DNAm数据的情况下具有广泛的适用性。
