Methylation of FKBP5 is associated with accelerated DNA methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged Black Americans.

Methylation of is involved in the regulation of the stress response and is influenced by early stress exposure. Two CpG sites, cg20813374 and cg00130530, have been identified as potential reporters of early stress. We examined whether methylation was associated with accelerated DNA methylation ageing and indirectly predicted poorer cardiovascular health among both young adult and middle-aged Black Americans. Four hundred and forty-nine young adults, with a mean age of 28.67 and N = 469 middle-age parents and their current partners with a mean age of 57.21, provided self-reports, biometric assessments, and blood draws. Methylation values were obtained using the Illumina Epic Array. Cardiometabolic risk was calculated by summing the standardized log-transformed scores for the body mass index, mean arterial blood pressure, and HbA1c. We also used a more standard index of risk, the Framingham 10-year cardiometabolic risk index, as an alternative measure of cardiometabolic risk. To measure accelerated ageing, four widely used indices of accelerated, DNA methylation-based ageing were used controlling sex, age, other variation in FKBP5, and cell-type. Exposure to community danger was associated with demethylation of methylation was significantly associated with accelerated ageing for both young-adult and middle-aged samples, with significant indirect effects from methylation to cardiometabolic risk through accelerated ageing for both. Early exposure to danger may influence methylation. In turn, methylation may help explain intrinsic accelerated ageing and elevated cardiometabolic risk in adulthood for Black Americans.