Whole-Genome Differentially Hydroxymethylated DNA Regions among Twins Discordant for Cardiovascular Death

We assessed whether DNA hydroxymethylation is prospectively associated with the risk for cardiovascular death independent of germline, age, and blood cell type composion. Overall design: Male twin pairs middle-aged in 1969-1973 and discordant for cardiovascular death through December 31, 2014 were included. Hydroxymethylation was quantified in buffy coat DNA collected in 1986–1987. Differentially hydroxymethylated regions (DhMRs) were identified after controlling for blood leukocyte subtypes and age among 12 monozygotic (MZ) pairs. The regions were used to create a binary linear classifier that predicted cardiovascular death among 19 dizygotic pairs.