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Comparative Study
. 2020 Jan 30;15(1):e0227728.
doi: 10.1371/journal.pone.0227728. eCollection 2020.

Associations between high blood pressure and DNA methylation

Nabila Kazmi  1   2 , Hannah R Elliott  1   2 , Kim Burrows  1   2 , Therese Tillin  3 , Alun D Hughes  3   4 , Nish Chaturvedi  3   4 , Tom R Gaunt  1   2   5 , Caroline L Relton  1   2   5
Affiliations
Comparative Study

Associations between high blood pressure and DNA methylation

Nabila Kazmi et al. PLoS One. .

Abstract

Background: High blood pressure is a major risk factor for cardiovascular disease and is influenced by both environmental and genetic factors. Epigenetic processes including DNA methylation potentially mediate the relationship between genetic factors, the environment and cardiovascular disease. Despite an increased risk of hypertension and cardiovascular disease in individuals of South Asians compared to Europeans, it is not clear whether associations between blood pressure and DNA methylation differ between these groups.

Methods: We performed an epigenome-wide association study and differentially methylated region (DMR) 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 (first generation migrants to the UK) from the Southall And Brent REvisited cohort, measuring DNA methylation from blood using the Illumina Infinium® HumanMethylation450 BeadChip.

Results: One CpG site was found to be associated with DBP in trans-ancestry analyses (i.e. both ethnic groups combined), while in Europeans alone 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 concordance between analyses. DMR analysis identified several 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 point to molecular pathways which may explain the elevated cardiovascular disease risk experienced by those of South Asian ancestry when compared to Europeans.

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Conflict of interest statement

TRG receives funding from GlaxoSmithKline, Biogen and Sanofi for research unrelated to the work presented here. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Manhattan plot indicating the associations between DBP and DNA methylation of men of European and South Asian ancestry.
The plot demonstrates the associations between DBP and DNA methylation of European and South Asian men collectively. The model was adjusted for confounders, estimated cell counts and principal components. The uncorrected log10(p-values) are plotted on the y-axis. The blue line is drawn to separate the CpG sites that surpassed p-value<1×10−05, a threshold for a suggestive association and the red line to separate the CpG sites that surpassed the Bonferroni-corrected threshold (p-value<1.24×10−07). The CpG sites that surpassed the Bonferroni-corrected threshold were considered to be associated with the trait.
Fig 2
Fig 2. A Manhattan plot indicating the associations between DBP and DNA methylation in European men.
The plot demonstrates the associations between DBP and DNA methylation in European men. The model was adjusted for confounders, estimated cell counts and principal components. The uncorrected–log10(p-values) are plotted on the y-axis. The blue line is drawn to separate the CpG sites that surpassed p-value<1×10−05, the threshold suggestive of an association and the red line to separate the CpG sites that surpassed the Bonferroni threshold (p-value<1.24×10−07). The CpG sites that surpassed the Bonferroni threshold were considered to be associated with the trait.
Fig 3
Fig 3. Consistency between fully adjusted EWAS of SBP, DBP and hypertension between Europeans and South Asian.
DNA methylation associations are shown for 402331 common CpG sites across three EWAS analyses. Each green dot represents a CpG site and the positions of the dots are determined by the effect size in each analysis. The grey lines on each dot denote the confidence intervals (CI) for the estimates. A linear fit of the overall correspondence summarises correlation between compared associations (green dashed line). Grey dashed line shows the line of equality in effect sizes between pairs of analyses. R2 = goodness of linear fit and as such is a measure of the consistency between two EWAS.
Fig 4
Fig 4. Venn diagrams to identify overlap between DMRs (mapped to genes) of DBP (A) and SBP (B) analyses conducted for South Asian and European groups.
SA denotes South Asian and Eu denotes European ancestry.
See this image and copyright information in PMC

References

    1. Krieger JE, Dzau VJ. Molecular biology of hypertension. Hypertension (Dallas, Tex: 1979). 1991;18(3 Suppl):I3–17. Epub 1991/09/01. 10.1161/01.hyp.18.3_suppl.i3 . - DOI - PubMed
    1. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet (London, England). 2012;380(9859):2224–60. Epub 2012/12/19. 10.1016/s0140-6736(12)61766-8 - DOI - PMC - PubMed
    1. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ (Clinical research ed). 2009;338:b1665 Epub 2009/05/21. 10.1136/bmj.b1665 - DOI - PMC - PubMed
    1. Eastwood SV, Tillin T, Chaturvedi N, Hughes AD. Ethnic Differences in Associations Between Blood Pressure and Stroke in South Asian and European Men. Hypertension (Dallas, Tex: 1979). 2015;66(3):481–8. Epub 2015/07/15. 10.1161/hypertensionaha.115.05672 - DOI - PMC - PubMed
    1. Zaman MJ, Bhopal RS. New answers to three questions on the epidemic of coronary mortality in south Asians: incidence or case fatality? Biology or environment? Will the next generation be affected? Heart (British Cardiac Society). 2013;99(3):154–8. Epub 2012/08/14. 10.1136/heartjnl-2012-302364 . - DOI - PubMed

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