Editors' ChoiceEpigenomics and Blood Pressure

DNA methylation: A link between genome variation and blood pressure

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Science Translational Medicine  14 Oct 2015:
Vol. 7, Issue 309, pp. 309ec176
DOI: 10.1126/scitranslmed.aad4446

Hypertension affects more than 1 billion people, causing ~9 million deaths each year from heart, kidney, and cerebrovascular disease. Kato et al. now report a genome-wide association and replication study of blood pressure phenotype in a very large, multi-ancestry cohort (320,251 individuals of East Asian, European, and South Asian ancestry in total). Their analysis revealed 12 new loci (SNPs) associated with blood pressure and a unique DNA methylation profile surrounding certain blood pressure–associated SNPs.

By using a conservative threshold for significance and careful replication in their association study, the authors found 12 new SNPs that were enriched in genes involved in vascular smooth muscle and renal functions. Interestingly, the sentinel SNP (the SNP with the lowest P value against any blood pressure phenotype tested) showed associated DNA methylation at multiple adjacent CpG sites, suggesting that genotype-dependent DNA methylation may be important for linking sequence variation to blood pressure. In a test of whether the DNA methylation was genotype-dependent or was a result of later environmental exposure, the authors were able to find the relationship between the SNPs and DNA methylation in newborns, before substantial adverse environmental exposure. This finding supported a causal relationship of the sentinel SNPs on blood pressure. The authors’ results suggest that DNA methylation may be involved in the regulatory pathway linking common genetic variants to blood pressure.

This article reports the largest genome-wide association study of blood pressure phenotype to date across three ancestral population groups. Their analysis identified new common blood pressure–associated loci where DNA methylation may play a critical role in gene regulation. The next step will be to test the association of rare genetic variants and blood pressure phenotypes.

N. Kato et al., Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation. Nat. Genet. 10.1038/ng.3405 (2015). [Abstract]

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