Background: High blood pressure is one of the major risk factors for cardiovascular disease and is influenced by both environmental and genetic factors. Epigenetic processes such as DNA methylation potentially mediate the relationship between genetic factors, the environment and cardiovascular disease. Despite an increased risk of cardiovascular disease in South Asians, it is not clear whether associations between blood pressure and DNA methylation differ between Europeans and South Asians.
Methods and Findings: In this study, we performed an epigenome-wide association study and differentially methylated region analysis to identify DNA methylation sites and regions that were associated with systolic blood pressure, diastolic blood pressure and hypertension. We analyzed samples from 364 European and 348 South Asian men from the Southall and Brent REvisited cohort, measuring DNA methylation from blood using the Illumina Infinium® HumanMethylation450 BeadChip. One CpG site was found to be associated with DBP in trans-ancestry analyses (i.e. both ethnic groups combined), while in Europeans seven CpG sites were associated with DBP. No associations were identified between DNA methylation and either SBP or hypertension. Comparison of effect sizes between South Asian and European EWAS for DBP, SBP and hypertension revealed little agreement between analyses. DMR analysis identified several DMRs including regions with known relationships with CVD and its risk factors.
Conclusion: This study identified differentially methylated sites and regions associated with blood pressure and revealed ethnic differences in these associations. These findings may uncover new molecular pathways which may explain differences in disease risk experienced by South Asians.
Nabila Kazmi*, Hannah R Elliott, Kim Burrows, Therese Tillin, Alun D Hughes, Nish Chaturvedi, Tom R Gaunt and Caroline L Relton
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