The Interplay of Epigenetic, Genetic, and Traditional Risk Factors on Blood Pressure: Findings from the Health and Retirement Study

The epigenome likely interacts with traditional and genetic risk factors to influence blood pressure. We evaluated whether 13 previously reported DNA methylation sites (CpGs) are associated with systolic (SBP) or diastolic (DBP) blood pressure, both individually and aggregated into methylation risk scores (MRS), in 3070 participants (including 437 African ancestry (AA) and 2021 European ancestry (EA), mean age = 70.5 years) from the Health and Retirement Study. Nine CpGs were at least nominally associated with SBP and/or DBP after adjusting for traditional hypertension risk factors (p < 0.05). MRS(SBP) was positively associated with SBP in the full sample (β = 1.7 mmHg per 1 standard deviation in MRS(SBP); p = 2.7 × 10(−5)) and in EA (β = 1.6; p = 0.001), and MRS(DBP) with DBP in the full sample (β = 1.1; p = 1.8 × 10(−6)), EA (β = 1.1; p = 7.2 × 10(−5)), and AA (β = 1.4; p = 0.03). The MRS and BP-genetic risk scores were independently associated with blood pressure in EA. The effects of both MRSs were weaker with increased age (p(interaction) < 0.01), and the effect of MRS(DBP) was higher among individuals with at least some college education (p(interaction) = 0.02). In AA, increasing MRS(SBP) was associated with higher SBP in females only (p(interaction) = 0.01). Our work shows that MRS is a potential biomarker of blood pressure that may be modified by traditional hypertension risk factors.