Navas-Acien A, Domingo-Relloso A, Subedi P, et al. - This multi-cohort prospective study demonstrated an association of blood DNA methylation with coronary heart disease (CHD) beyond conventional factors linked with cardiovascular disease, with a complex epigenomic signature across populations.

• A high burden of CHD exists in American Indian communities.

• In 4 US states, 12 American Indian communities were assessed.

• 505 differentially methylated positions (DMPs) linked with incident CHD were selected in the Strong Heart Study, using a high-dimensional multi-adjusted model.

• Evaluation of these DMPs was done in the Women’s Health Initiative, the Framingham Heart Study, and the Atherosclerosis Risk in Communities Study.

• Various DMPs common across cohorts tagged genes with established links with cardiovascular disease.