The applicability of DNA methylation-based tools in a low-income, sub-Saharan African population: Malawi longitudinal study of families and health

Abstract

Summary DNA methylation (DNAm)-based tools are predominantly developed in European ancestry, high-income populations, raising questions on their applicability in diverse and rural settings. To evaluate these tools in a sub-Saharan African low-income context, we analyzed genome-wide DNAm data from 49 dried blood spot samples from adults aged 45+ years in the Malawi Longitudinal Study of Families and Health (MLSFH). Leveraging varying field and storage conditions inherent to this rural setting, we examined their impact on DNAm and found no significant contribution to genome-wide DNAm or predictive sites used in these tools. DNAm-derived estimates of epigenetic clocks and lifestyle biomarkers showed modest to high correlations with self-reported measures. Known associations of epigenetic age acceleration with adverse health behaviors were validated. DNAm-based immune cell type proportions aligned with expected cell-type changes in aging and human immunodeficiency virus. Our findings lay the groundwork for broader use of DNAm-based tools in sub-Saharan African populations.