Abstract P394: BIUXX

Mediating effects of body mass index on the association between DNA methylation regions and 24-hour blood pressure Xiaoqing Pan, Yong Liu, Yuru Chen, Yifan Yang, Srividya Kidambi, Mingyu Liang, Pengyuan Liu Background: Recent studies have highlighted the significant role of DNA methylation in blood pressure (BP) regulation and hypertension development. In addition to epigenetics, it is well known that obesity is one of the major lifestyle factors closely associated with hypertension. However, no studies have evaluated the indirect effect of DNA methylation on 24-hour BP measurements through obesity-related phenotypes such as body mass index (BMI). Methods: Causal mediation analysis was applied to examine the mediating effects of BMI on the association between DNA methylation and 24-hour BP phenotypes, including systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP), in 281 black participants. Results: Reanalysis of 38,215 DNA methylation regions (MRs), derived from 1,549,368 CpG sites across the genome, identified up to 138 MRs that were significantly associated with 24-hour BP measurements through the mediator of BMI. Among them, 38 (19.2%) of these MRs were simultaneously associated with SBP, DBP and MAP. Genes associated with BMI-mediated MRs are potentially involved in multiple chronic diseases such as coronary artery disease and renal disease, of which hypertension is a well-known major risk factor. In particular, 3 genes (CDH4, NOTCH1 and COLGALT1) were significantly associated with 24-hour BP measurements directly and indirectly through BMI after adjusting for covariates of age and sex. Conclusions: Our findings suggest that in addition to its direct involvement, DNA methylation may mediate the development of hypertension through BMI.