DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins.

Obesity is an established risk factor for hypertension, but the mechanisms are only partially understood. We examined whether body mass index (BMI)-related DNA methylation (DNAm) variation would mediate the association of BMI with blood pressure (BP). We first conducted a genomewide DNA methylation analysis in monozygotic twin pairs to detect BMI-related DNAm variation and then evaluated the mediating effect of DNAm on the relationship between BMI and BP levels using the causal inference test (CIT) method and mediation analysis. Ontology enrichment analysis was performed for CpGs using the GREAT tool. A total of 60 twin pairs for BMI and systolic blood pressure (SBP) and 58 twin pairs for BMI and diastolic blood pressure (DBP) were included. BMI was positively associated with SBP (β = 1.86, = .0004). The association between BMI and DNAm of 85 CpGs reached < 1×10 level. Eleven BMI-related differentially methylated regions (DMRs) within , , , , , , , , , and were found. Of the 85 CpGs, 9 mapped to , , , , , and were significantly associated with SBP levels. Of the 9 CpGs, 2 within negatively mediated the association between BMI and SBP, with a mediating effect of -0.24 (95% CI [-0.65, -0.01]). BMI was also positively associated with DBP (β = 0.60, = .0495). The association between BMI and DNAm of 193 CpGs reached < 1×10 level. Twenty-five BMI-related DMRs within , , , , , , and were found. Of the 193 CpGs, 33 mapped to , , , , , , and were significantly associated with DBP levels. Of the 33 CpGs, 12 within , , , , , , and negatively mediated the association between BMI and DBP, with a total mediation effect of -0.66 (95% CI [-1.07, -0.30]). Interestingly, BMI might also negatively mediate the association between the DNAm of most CpG mediators mentioned above and BP. The mediating effect of DNAm was also found when stratified by sex. In conclusion, DNAm variation may partially negatively mediate the association of BMI with BP. Our findings may provide new clues to further elucidate the pathogenesis of obesity to hypertension and identify new diagnostic biomarkers and therapeutic targets for hypertension.