Figure 3.

Illustration of the Relationship of Methylation at cg23999170 with Diastolic BP, Mediated by Expression of TSPAN2

Methylation at cg23999170 was identified as associated with diastolic BP in discovery and replication meta-analyses of genome-wide DNA methylation (N = 17,010). Expression of TSPAN2 was associated with methylation at cg23999170 in meta-analyses of FHS and RS and diastolic BP in FHS. The direction of arrows in the diagram are inferred from significant two-step Mendelian randomization using data from the Genotype-Tissue Expression project and International Consortium for Blood Pressure, which suggests that methylation at cg23999170 influences BP through the expression of TSPAN2. The epigenome-wide association of DNA methylation and diastolic BP is interpreted given the evidence of causal direction and based on a 0.1% change in DNA methylation at cg23999170. Abbreviation: DBP, diastolic blood pressure.